On November 4, 2021 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a global biotechnology company focused on developing and commercializing innovative medicines worldwide, reported recent business highlights, anticipated upcoming milestones, and financial results for the third quarter and nine months ended September 30, 2021 (Press release, BeiGene, NOV 4, 2021, View Source [SID1234594440]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We remain focused on translating science into highly impactful medicines and making these medicines more affordable and accessible to many more people with cancer around the world"

"We remain focused on translating science into highly impactful medicines and making these medicines more affordable and accessible to many more people with cancer around the world," said John V. Oyler, Co-Founder, Chairman and Chief Executive Officer of BeiGene. "In the third quarter we had two new indications approved for BRUKINSA in the United States, and recent BRUKINSA approvals in Australia, Singapore, Brazil, Russia, and Chile as well as a positive CHMP opinion for our first BRUKINSA filing in Europe. Tislelizumab’s BLA for esophageal squamous cell carcinoma (ESCC) has been accepted for review by the FDA, which is the first filing for our internally developed anti-PD-1 medicine outside of China and an important achievement in our collaboration with Novartis. This is one of many global tislelizumab studies that comprise a comprehensive PD-1 program that has enrolled over 5,600 patients in more than 30 countries and regions and includes over 1,700 patients from outside of China. We also continued to expand and strengthen our strategic competitive advantages that we feel are critical to transform the industry and bring innovative and accessible medicines to billions more people around the world. These include research, predominantly CRO-free global clinical development, global commercial infrastructure, and internal manufacturing capabilities."

Recent Business Highlights and Upcoming Milestones

Commercial Operations

Product sales increased 111% in the third quarter of 2021 compared to the prior year period, primarily due to increased sales of our internally developed products and in-licensed products from Amgen;
Global sales of BRUKINSA totaled $65.8 million in the third quarter, representing a 320% increase compared to the prior year period; U.S. sales of BRUKINSA totaled $33.7 million in the third quarter compared to $5.7 million in the comparable prior year period. U.S. sales continued to accelerate in the quarter, driven by continued uptake in mantle cell lymphoma (MCL) and the recent FDA approvals in Waldenström’s macroglobulinemia (WM) and marginal zone lymphoma (MZL). BRUKINSA sales in China totaled $32.1 million in the third quarter, representing growth of 223% compared to the prior year period, driven by a significant increase in all approved indications, including chronic lymphocytic leukemia (CLL);
Sales of tislelizumab in China totaled $77.0 million in the third quarter, representing a 54% increase compared to the prior year period. In the third quarter, new patient demand from broader reimbursement and further expansion of our salesforce and hospital listings continued to drive increased market penetration and market share for tislelizumab;
The commercial organization in China continued to demonstrate its ability to bring new products to market, launching the second product from the Amgen collaboration, BLINCYTO (blinatumomab), which contributed $5.0 million of sales in the third quarter. Two additional new products are expected to be approved or launched by the end of the year; and
We are preparing for the upcoming National Reimbursement Drug List (NRDL) negotiation in China for our eligible medicines, including tislelizumab in first-line non-squamous non-small cell lung cancer (NSCLC), first-line squamous NSCLC and second- or third-line hepatocellular carcinoma (HCC), BRUKINSA in WM, and pamiparib in germline BRCA (gBRCA) mutation-associated recurrent advanced ovarian, fallopian tube, or primary peritoneal cancer who have been treated with two or more lines of chemotherapy. The NRDL negotiations are anticipated to be completed in the fourth quarter of 2021.
Development Programs

BRUKINSA (zanubrutinib), a small molecule inhibitor of Bruton’s tyrosine kinase (BTK) designed to maximize BTK occupancy and minimize off-target effects, approved in the U.S., China, Canada, Australia, and other international markets in selected indications and under development for additional approvals globally.

Received FDA approvals in two new indications, including full approval for the treatment of adult patients with WM, and accelerated approval for the treatment of adult patients with relapsed or refractory (R/R) marginal zone lymphoma (MZL) who have received at least one anti-CD20-based regimen;
Received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA), recommending approval for the treatment of adult patients with WM who have received at least one prior therapy or first-line treatment for patients unsuitable for chemo-immunotherapy;
Was granted a cohort Temporary Authorization for Use (cATU), an early access program, for patients with WM by the French National Agency for Medicines and Health Products Safety (ANSM);
Received acceptance of the marketing authorization application (MAA) from Swissmedic and the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK for patients with WM;
Received approval in Australia for the treatment of adult patients with MCL who have received at least one prior therapy and for patients with WM who have received at least one prior therapy or in first line treatment for patients unsuitable for chemo-immunotherapy; and
Continued to advance BRUKINSA in new markets. BRUKINSA is now approved in Australia, Russia, Singapore, Brazil, Chile, Israel, and UAE for patients with MCL who have received at least one prior therapy. There currently are more than 20 marketing authorization applications in multiple indications under review around the world.
Expected Milestones for BRUKINSA

Receive EMA approval for treating adult patients with WM who have received at least one prior therapy or first-line treatment for patients unsuitable for chemo-immunotherapy in 2021;
Report results from the Phase 3 SEQUOIA trial (NCT03336333) comparing BRUKINSA with bendamustine plus rituximab in patients with treatment-naïve CLL or small lymphocytic lymphoma (SLL); and early results from Arm D in patients with del(17p) in combination with venetoclax in two oral presentations at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting taking place December 11-14, 2021;
Continue to discuss Phase 3 clinical trial results in CLL with regulatory agencies in the U.S., Europe, and other countries;
Report additional results from the Phase 3 ALPINE trial (NCT03734016) in 2022; and
Continue to expand BRUKINSA’s registration program globally in new geographies and indications, including potential additional approvals in 2021 and the first half of 2022 for certain patients with MCL in APAC, the Middle East and South America.
Tislelizumab, a humanized IgG4 anti-PD-1 monoclonal antibody specifically designed to minimize binding to FcγR on macrophages; approved in China in selected indications and under development for additional approvals globally.

Received acceptance by the FDA of a BLA for tislelizumab in collaboration with Novartis as a treatment for patients with unresectable recurrent locally advanced or metastatic ESCC after prior systemic therapy. The Prescription Drug User Fee Act (PDUFA) target action date is July 12, 2022;
Received acceptance by the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) of a supplemental BLA (sBLA) in combination with chemotherapy as a first-line treatment for patients with recurrent or metastatic nasopharyngeal cancer (NPC);
Received approval from the NMPA in a new indication, for front-line squamous NSCLC with nab-paclitaxel and carboplatin; and
Reported data at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2021 including:
– RATIONALE 304 (NCT03663205): Tislelizumab plus chemotherapy vs. chemotherapy alone as first-line treatment for non-squamous NSCLC in patients who are smokers vs. non-smokers; and

– RATIONALE 307 (NCT03594747): Tislelizumab plus chemotherapy vs. chemotherapy alone as first-line treatment for advanced squamous NSCLC in patients who were smokers vs. non-smokers.

Expected Milestones for Tislelizumab

Receive approvals in China for the four sBLAs currently under review in first-line NPC, second- or third-line NSCLC, second-line ESCC, and second- or third-line MSI-High solid tumors in 2022.
Pamiparib, a selective small molecule inhibitor of PARP1 and PARP2 conditionally approved in China for the treatment of patients with germline BRCA mutation-associated advanced ovarian, fallopian tube, or primary peritoneal cancer who have been treated with two or more lines of chemotherapy.

Expected Milestones for Pamiparib

Report topline results from the Phase 3 trial (NCT03519230) of pamiparib as a maintenance treatment in patients with platinum-sensitive recurrent ovarian cancer, in 2021 or the first half of 2022.
Ociperlimab (BGB-A1217), an investigational anti-TIGIT monoclonal antibody with competent Fc function

Initiated patient enrollment in the Phase 2 AdvanTIG-206 trial (NCT04948697) of ociperlimab in combination with tislelizumab plus Bio-Thera’s POBEVCY (BAT1706), a biosimilar to bevacizumab (Avastin), as first-line treatment in patients with advanced HCC.
Expected Milestones for ociperlimab

Initiate patient enrollment in the global Phase 2 AdvanTIG-205 trial (NCT05014815) in frontline stage IV NSCLC, in 2021.
BGB-11417, an investigational BCL-2 inhibitor

Initiated patient enrollment in a Phase 1 trial (NCT04973605) in patients with multiple myeloma with t (11;14) translocation, in 2021.
Expected Milestones for BGB-11417

Begin patient enrollment in pivotal trials, in 2022.
Early-Stage Programs

Continued to advance our early-stage clinical pipeline of internally-developed product candidates at dose escalation stage, including BGB-A445 (an investigational non-ligand competing OX40 monoclonal antibody as monotherapy or in combination with tislelizumab in solid tumors), BGB-15025 (an investigational hematopoietic progenitor kinase 1 (HPK1) inhibitor as monotherapy or in combination with tislelizumab in solid tumors), BGB-10188 (an investigational PI3Kδ inhibitor as monotherapy or in combination with BRUKINSA in hematology malignancies, or in combination with tislelizumab in solid tumors);
BGB-16673 (an investigational Chimeric Degradation Activating Compound, or CDAC, targeting BTK) received investigational new drug (IND) clearance and permission to proceed from the FDA. Patient dosing in the first Phase 1 trial (NCT05006716) in patients with B-cell malignancies is expected to begin in 2021; and
BGB-A425 (an investigational TIM3 monoclonal antibody) study advanced to the Phase 2 portion of the Phase 1/2 trial (NCT03744468) in combination with tislelizumab.
Collaboration with Amgen

Secured approval by the Hainan BoAo government for early access to LUMAKRAS (sotorasib, a KRAS G12C inhibitor) in designated hospitals in the province.
Other Collaboration Programs

Announced that the NMPA granted QARZIBA (dinutuximab beta) conditional approval for the treatment of high-risk neuroblastoma in patients aged 12 months and above who have previously received induction chemotherapy and achieved at least a partial response, followed by myeloablative therapy and stem cell transplantation, as well as patients with a history of R/R neuroblastoma with or without residual disease. QARZIBA is a targeted immunotherapy licensed by EUSA Pharma to BeiGene in mainland China;
Received notification by BMS-Celgene of its intent to terminate a license and supply agreement with respect to ABRAXANE (nanoparticle albumin-bound paclitaxel) in China. BeiGene contests this action, as it believes that the reasons provided by BMS-Celgene are not valid bases for terminating the agreement with respect to ABRAXANE. Arbitration proceedings are ongoing between the parties regarding BMS-Celgene’s failure to ensure the continuity and adequacy of its supply of ABRAXANE under the agreement in accordance with Good Manufacturing Practices (GMP); and
Received results from the Phase 2 trial (NCT04551898) evaluating investigational SARS-CoV-2 neutralizing antibody BGB-DXP593 in patients with mild to moderate COVID-19, licensed from Singlomics outside of China. The trial did not meet the primary efficacy endpoint of viral load change in nasopharyngeal swabs at Day 8. The license rights of the two Singlomics candidates (DXP593 and DXP604) outside of the U.S. and the development rights of the candidates in the U.S. have been returned to Singlomics under a reversion agreement signed by the parties, with BeiGene retaining U.S. commercial rights.
Sitravatinib, an investigational tyrosine kinase inhibitor of receptor tyrosine kinases (RTKs), including TAM family receptors (TYRO3, Axl, MER), split family receptors (VEGFR2, KIT) and RET, licensed from Mirati Therapeutics Inc. (Mirati), in Asia (excluding Japan), Australia, and New Zealand.

Reported data at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2021:
− Sitravatinib + tislelizumab in patients with anti-PD-(L)1 refractory/resistant metastatic NSCLC (NCT03666143); and

− Sitravatinib + tislelizumab in patients with metastatic NSCLC (NCT03666143).

Zanidatamab, (ZW25) an investigational bispecific HER2 antibody targeting HER2 in late-stage clinical development with Zymeworks, Inc.

Expected Milestones for Zanidatamab

Initiate a Phase 3 clinical trial in first-line HER2+ gastric cancer, in 2021.
Manufacturing Operations

Continued efforts to secure geographically diverse manufacturing and supply chain redundancy with the previously announced plans to build a new commercial-stage manufacturing and clinical R&D campus at Princeton West Innovation Park in Hopewell, New Jersey. The acquisition of the property is expected to close in 2021;
Continued construction on the new small molecule manufacturing campus in Suzhou, China. Phase 1 of construction will bring over 50,000 square meters and 600M solid preparation capacity and is expected to be completed in 2023. Once completed, the total production capacity is expected to increase BeiGene’s small molecule manufacturing capability in China by up to six times the current capacity; and
Two additional 2,000L bioreactors at Boehringer Ingelheim’s facility are available to support commercial production of tislelizumab’s expanding indications in China. This is in addition to BeiGene’s state-of-the-art biologics facility in Guangzhou, China, which currently is approved for 8,000 liters of biologics capacity with an additional phase of construction expected to bring total capacity to 64,000 liters, and to be completed by the end of 2022.
COVID-19 Impact and Response

The Company expects that the worldwide health crisis of COVID-19 will continue to have a negative impact on its operations, including commercial sales, regulatory interactions, inspections, filings, and clinical trial recruitment, participation, and data read outs. There remains uncertainty regarding the future impact of the pandemic globally. The Company is striving to minimize delays and disruptions, and continues to execute on its commercial, regulatory, manufacturing, and clinical development goals globally.
Corporate Developments

Listing of the Company’s ordinary shares on the Science and Technology Innovation Board (STAR Market) of the Shanghai Stock Exchange is expected to be completed in 2021, subject to market conditions and additional regulatory approvals; and
Received inclusion in several FTSE Russell indices, including: the FTSE Global Equity Index Large Cap; the FTSE All-World (LM); the FTSE All-Cap (LMS); and the FTSE Total-Cap (LMSµ). In addition, BeiGene was included in the FTSE Developed ESG Low Carbon Select Index, and the FTSE Asia ex Japan ESG Low Carbon Select Index, reflecting the Company’s commitment to sustainability.
Third Quarter 2021 Financial Results

Cash, Cash Equivalents, Restricted Cash, and Short-Term Investments were $3.9 billion as of September 30, 2021, compared to $4.4 billion as of June 30, 2021, and $4.7 billion as of December 31, 2020.

In the three months ended September 30, 2021, cash used in operating activities was $495.7 million, primarily due to our net loss of $413.9 million and a $89.4 million increase in our net operating assets and liabilities, offset by non-cash charges of $7.5 million; capital expenditures were $67.0 million; and cash provided by financing activities was $109.2 million, consisting primarily of $50 million in proceeds from the sale of shares to Amgen, as well as the exercise of employee share options.
Revenue for the three months ended September 30, 2021 was $206.4 million, compared to $91.1 million in the same period of 2020.

Product revenue totaled $192.5 million for the three months ended September 30, 2021, compared to $91.1 million in the same period of 2020, including:
– Sales of tislelizumab in China of $77.0 million, compared to $49.9 million in the prior year period;

– Sales of BRUKINSA of $65.8 million, compared to $15.7 million in the prior year period;

– Sales of XGEVA (denosumab), the first product transferred to BeiGene from the Amgen collaboration, in China of $15.7 million, compared to $3.1 million in the prior year period. BeiGene commenced sales and marketing in China in July 2020;

Collaboration revenue for the three months ended September 30, 2021 was $14.0 million, resulting from the partial recognition of previously deferred revenue associated with the upfront payment received from Novartis in the first quarter of 2021. There was no collaboration revenue in the prior year period.
Expenses for the three months ended September 30, 2021 were $668.8 million, compared to $531.2 million in the same period of 2020.

Cost of Sales for the three months ended September 30, 2021 were $47.4 million, compared to $21.1 million in the same period of 2020. Cost of sales increased primarily due to increased product sales of tislelizumab, BRUKINSA, and XGEVA.
R&D Expenses for the three months ended September 30, 2021 were $351.9 million, compared to $349.1 million in the same period of 2020. The increase in R&D expenses was primarily attributable to increases in headcount and external costs related to our investment in discovery and development activities, including our continued efforts to internalize research and clinical trial activities, partially offset by decreased spending on clinical trials related to BRUKINSA, as well as decreased expense related to upfront fees related to in-process R&D. Additionally, R&D-related share-based compensation expense was $31.7 million for the three months ended September 30, 2021, compared to $25.4 million for the same period of 2020.
SG&A Expenses for the three months ended September 30, 2021 were $269.2 million, compared to $160.8 million in the same period of 2020. The increase in SG&A expenses was primarily attributable to increased headcount and increased external expenses related to the growth of our global commercial organization, as we continued to build our worldwide footprint. SG&A-related share-based compensation expense was $35.4 million for the three months ended September 30, 2021, compared to $24.9 million for the same period of 2020.
Net Loss for the three months ended September 30, 2021 was $413.9 million, or $0.34 per share, and $4.46 per American Depositary Share (ADS), compared to $425.2 million, or $0.37 per share, and $4.81 per ADS in the same period of 2020.

On November 4, 2021 Athenex, Inc., (NASDAQ: ATNX), a global biopharmaceutical company dedicated to the discovery, development, and commercialization of novel therapies for the treatment of cancer and related conditions, reported a corporate and financial update for the third quarter ended September 30, 2021 (Press release, Athenex, NOV 4, 2021, View Source [SID1234594456]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Following our recent Type A meeting with U.S. FDA to discuss our New Drug Application for oral paclitaxel and encequidar (Oral Paclitaxel) in metastatic breast cancer, we determined that deploying our resources towards other ongoing clinical programs of Oral Paclitaxel and our cell therapy programs would be a better way to maximize value for all of our shareholders and stakeholders," said Johnson Lau, Chief Executive Officer of Athenex. "Our management team is focused on advancing the clinical pipeline where we believe Athenex has a strong competitive advantage, as well as exploring various other approaches for our assets that will unlock shareholder value. We are particularly pleased with the continued positive momentum and increasing visibility of our cell therapy programs."

Third Quarter 2021 and Recent Business Highlights

Clinical Programs

Orascovery

Held a Type A meeting with the U.S. Food and Drug Administration (FDA) regarding the New Drug Application (NDA) for Oral Paclitaxel in metastatic breast cancer.
Presented positive interim data from a Phase 1 trial evaluating Oral Paclitaxel in combination with pembrolizumab in patients with advanced solid malignancies at ESMO (Free ESMO Whitepaper) 2021.
Received confirmation from the Innovative Licensing and Access Pathway (ILAP) in the UK that encequidar in combination with oral anticancer medicines has been awarded the innovative medicine designation, the Innovation Passport. ILAP was set up by the UK Medicines & Healthcare products Regulatory Agency (MHRA) and other UK government agencies to efficiently accelerate the time to market and facilitating patient access to innovative medicines.
Cell Therapy

Interim data from the ongoing Phase 1 ANCHOR trial evaluating KUR-502 in patients with CD19-positive relapsed or refractory lymphoma and leukemia have been accepted for poster presentation at the 2021 ASH (Free ASH Whitepaper) Annual Meeting.
The U.S. Patent and Trademark Office allowed patent claims around the NKT cellular immunotherapy platform developed by Athenex and the Center for Cell and Gene Therapy at Baylor College of Medicine, Texas Children’s Hospital and Houston Methodist Hospital.
Opened enrollment in Phase 1 trial to evaluate TCRT-ESO-A2 (high-affinity TCR-T targeting NY-ESO-1 solid tumors).
Commercial Update

Klisyri (tirbanibulin)

Athenex’s partner, Almirall (Almirall, S.A., BME: ALM), launched Klisyri (tirbanibulin) in Germany and the UK. Klisyri received approval by the European Commission and the UK MHRA in July and August of 2021, respectively, for the topical treatment of actinic keratosis (AK) of the face and scalp in adults.
Specialty Pharmaceutical Business

Athenex Pharmaceutical Division (APD) currently markets a total of 33 products with 64 SKUs.
Athenex Pharma Solutions (APS) currently markets 5 products with 16 SKUs.
Corporate

Dr. Michael Smolinski promoted to Chief Scientific Officer. Dr. Smolinski has been with Athenex for 13 years and previously served as Vice President of Preclinical Operations.
Key Anticipated Milestones

ANCHOR Phase 1 poster presentation at 2021 ASH (Free ASH Whitepaper) in December
Results from the I-SPY 2 trial of oral paclitaxel plus anti PD-1 expected in 2022
Almirall to continue phased roll-out of Klisyri in other European countries in 2022
Third Quarter 2021 Financial Highlights

Revenues from product sales increased to $27.0 million for the three months ended September 30, 2021, from $24.8 million for the three months ended September 30, 2020, an increase of $2.2 million or 9%. This increase was primarily attributable to an increase in 503B product sales of $2.1 million as the result of the increase in demand for certain drugs used to treat patients hospitalized with COVID-19. API product sales and contract manufacturing sales each experienced an increase of $0.4 million. These increases were offset by a decrease in APD product sales of $0.7 million, resulting primarily from a significant prior year increase in demand for COVID-19 related drugs and for FDA shortage products during 2020, including some significant non-recurring orders.

License fees and other revenue decreased by $5.4 million, for the three months ended September 30, 2021. This decrease was primarily due to the recognition of $5.1 million in license and royalty revenue from Almirall for the launch of Klisyri in Europe in September 2021, while we recognized $10.4 million in license revenue during the three months ended September 30, 2020, pursuant to license agreements with Xiangxue and PharmaEssentia.

Cost of sales for the three months ended September 30, 2021 totaled $25.6 million, an increase of $1.1 million, or 5%, as compared to $24.5 million for the three months ended September 30, 2020. The increase was primarily due to an increase of $2.9 million in cost of 503B product sales as production levels increased. Cost of APD product sales increased by $0.9 million, while the cost of API product sales decreased by $0.1 million. Additionally, cost of sales related to royalties for license income decreased by $2.5 million due to the royalty payment that incurred in 2020 on the license revenue from Xiangxue.

R&D expenses for the three months ended September 30, 2021 totaled $17.7 million, a decrease of $0.7 million, or 4%, as compared to $18.4 million for the three months ended September 30, 2020. This was primarily due to a decrease in costs of clinical operations of $2.4 million after the completion of the Phase 3 studies for tirbanibulin ointment and Oral Paclitaxel, a decrease in Oral Paclitaxel product development and medical affairs costs of $1.8 million incurred in connection with the potential product launch, a decrease in costs of preclinical operations of $1.0 million, and a decrease in R&D related compensation expenses of $0.4 million. The decrease in these R&D expenses was partially offset by a $2.6 million increase in cell therapy development costs, a $2.0 million increase in drug licensing costs related to licenses for specialty drug products, and a $0.3 million increase in costs of other product development.

SG&A expenses for the three months ended September 30, 2021 totaled $22.8 million, an increase of $0.6 million, or 3%, as compared to $22.2 million for the three months ended September 30, 2020. This was primarily due to a $3.2 million increase from the change in fair value of contingent consideration, a $2.1 million increase in operating costs including insurance and IT costs and professional fees, a $1.9 million increase in compensation related costs, and a $1.1 million increase in site preparation costs related to the manufacturing facility in Dunkirk. The increase was partially offset by a $7.7 million decrease in costs for preparing to commercialize Oral Paclitaxel as significant pre-launch activities occurred in 2020 and slowed upon receipt of the Complete Response Letter in February 2021.

Interest expense totaled $5.1 million and $3.6 million for the three months ended September 30, 2021 and 2020, respectively. Interest expense in the current period was incurred from the Senior Credit Agreement with Oaktree, while interest expense in the prior period was primarily incurred from debt under a former credit agreement with Perceptive Advisors LLC and its affiliates.

Income tax expense for the three months ended September 30, 2021 amounted to $0.3 million, compared to income tax expense of $1.1 million for the same period in 2020. The income tax expense in the prior year was primarily attributable to foreign income tax withholdings on our revenue earned under our out-license arrangements.

Net loss attributable to Athenex for the third quarter was $36.1 million or 33 cents per diluted share, as compared to a net loss of $36.8 million or 44 cents per diluted share, for the same period in 2020.

For further details on the Company’s financial results, including the results for the nine months ended September 30, 2021, refer to the Form 10Q filed with the SEC.

Financial Guidance

In terms of product sales guidance, the Company is limiting financial guidance to the existing Athenex product portfolio only. In 2020, the Company recorded a significant amount of revenues from international customers as a result of the global pandemic. However, it does not see these revenues as recurring in nature. In the first nine months of 2021, the Company experienced significant COVID-related challenges in our Indian supply chain and to a lesser extent China, which slowed down APD product sales during the period. As a result, the Company now expects its full year product sales in 2021, excluding any royalties from Klisyri, to decline by 6% to 12% year-over-year compared with 2020 levels.

Cash Conservation Update

As of September 30, 2021, the company had cash and cash equivalents of $73.6 million, restricted cash of $16.5 million, and short-term investments of $14.9 million, for a total of $105.0 million. Given the earlier uncertainty stemming from the CRL for Oral Paclitaxel in metastatic breast cancer, the Company has already identified and adopted certain cash conservation measures. The Company is seeking additional cash conservation and funding opportunities to further extend the cash runway.

Conference Call and Webcast Information

Athenex will host a conference call and live audio webcast today, Thursday, November 4, 2021, at 10:00 am Eastern Time to discuss the financial results and provide a business update.

To participate in the call, dial either the domestic or international number fifteen minutes before the conference call begins:

On November 4, 2021 Sarepta Therapeutics, Inc. (NASDAQ:SRPT), the leader in precision genetic medicine for rare diseases, reported financial results for the third quarter of 2021 (Press release, Sarepta Therapeutics, NOV 4, 2021, View Source [SID1234594473]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are pleased to report another quarter of strong performance serving the Duchenne community with our three currently approved therapies and on that basis have once again raised our full-year product revenue guidance. In total, we have raised guidance by some $70 million this year and are now guiding to $605 million to $615 million. This represents our 20th straight quarter of strong revenue growth and we anticipate this growth continuing in 2022," said Doug Ingram, president and chief executive officer, Sarepta. "We have now initiated Part B of MOMENTUM, our pivotal trial for SRP-5051, our next-generation PPMO candidate for exon 51 skip amenable Duchenne patients as well as EMBARK, our pivotal trial for SRP-9001, our micro-dystrophin gene therapy for Duchenne. Also, this quarter we shared additional compelling data across three studies for SRP-9001, providing additional conviction as we execute on EMBARK and prepare to unblind and release Study 102 Part 2 results in the first quarter of next year. As we track out of 2021 and into a milestone-rich 2022, we are delivering on our approved therapies, seeing successes across our programs, and as of today, with greater than $2 billion of cash and cash equivalents on our balance sheet and a first-in-class team of genetic and rare disease professionals, have the resources and talent to deliver on the promise of our multi-platform pipeline."

Third Quarter 2021 and Recent Corporate Developments:

At SRP-9001 Micro-dystrophin R&D Day Sarepta showed sustained functional improvements in multiple studies of individuals with Duchenne: In October of 2021, the Company presented new analyses and functional data from its SRP-9001 development program and details of EMBARK (Study SRP-9001-301); its global pivotal Phase 3 trial of SRP-9001 for the treatment of Duchenne. SRP-9001 is an investigational gene transfer therapy intended to deliver its micro-dystrophin-encoding gene to muscle tissue for the targeted production of the micro-dystrophin protein. The results presented highlight the breadth, depth and strength of the clinical evidence to date for SRP-9001 in treating Duchenne.
SRP-9001-101 (Study 101): Results from participants treated with SRP-9001 in Study 101 (n=4, ages 4 to 7) found that participants improved 8.6 points on the North Star Ambulatory Assessment (NSAA) compared to a matched natural history cohort three years following a single administration of SRP-9001 (p<0.0001).
SRP-9001-102 (Study 102): The results from Study 102 Part 1 found that SRP-9001-treated participants (n=12, ages 6 to 7) had a positive 2.9-point difference on NSAA compared to a matched natural history cohort one year after treatment (p=0.0129).
ENDEAVOR, SRP-9001-103 (Study 103): The first functional results presented from Study 103, which uses commercially representative SRP-9001 material, the first 11 participants in Cohort 1, ages 4 to 7, demonstrated a 3.0-point improvement from baseline on NSAA six months after treatment.
Across three clinical studies, the tolerability profile remains consistent in all treated patients.

Initiated EMBARK (Study SRP-9001-301), the first global pivotal study of SRP-9001 for the treatment of Duchenne: The EMBARK study is a multi-center clinical trial initiating in the US, Europe and Asia. It is the first global, randomized, double-blind, placebo-controlled clinical trial of commercially representative SRP-9001 material and will enroll 120 participants with Duchenne between the ages of 4 to 7. The primary endpoint will assess the change in NSAA total score from baseline to week 52 compared to placebo. Key features include stratification of participants by age and baseline NSAA, with a minimum of 50 percent of patients ages 4 to 5 to be enrolled. Inclusion criteria include a Time to Rise from Floor of less than 5 seconds, a stable daily dose of oral corticosteroids for at least 12 weeks before screening and rAAVrh74 antibody titers of less than 1:400. Participants with mutations between or including exons 1-17 or mutations fully contained within exon 45 (inclusive) are not eligible. The Company expects the trial to fully enroll in the first half of 2022.

Initiated Part B of MOMENTUM (Study SRP-5051-201) in patients with Duchenne amenable to exon 51 skipping: In the fourth quarter of 2021, the Company initiated Part B of MOMENTUM, a global trial investigating the use of SRP-5051, the Company’s next-generation peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) to treat patients with Duchenne who are amenable to exon 51 skipping. The study plans to enroll between 20-40 patients between ages 7 to 21 amenable to exon 51 skipping who are naïve to SRP-5051. Additionally, those previously dosed in Study 5051-201, Part A or Study 5051-102 who meet the entrance criteria will be eligible to participate. Both ambulatory and non-ambulatory patients are eligible for participation. Sarepta anticipates Part B of MOMENTUM to serve as a pivotal study for SRP-5051 and plans to seek Accelerated Approval if the trial is successful.

Showcased data from gene therapy and RNA platforms at World Muscle Society (WMS) 2021 Virtual Congress: Sarepta’s presentations at WMS 2021 highlighted scientific leadership and innovation from across the Company’s deep, multi-platform portfolio and reflect a continued commitment to advancing life-changing therapies for those with rare genetic diseases. Notably, new research was presented on the prevalence of pre-existing antibodies to the AAVrh74 vector, which is used in several of Sarepta’s gene transfer therapy programs. The posters are available on the Investor Relations section of www.sarepta.com.
Conference Call
The Company will be hosting a conference call at 4:30 p.m. Eastern Time to discuss Sarepta’s financial results and provide a corporate update. The conference call may be accessed by dialing (844) 534-7313 for domestic callers and (574) 990-1451 for international callers. The passcode for the call is 7131019. Please specify to the operator that you would like to join the "Sarepta Third Quarter 2021 Earnings Call." The conference call will be webcast live under the investor relations section of Sarepta’s website at www.sarepta.com and will be archived there following the call for 90 days. Please connect to Sarepta’s website several minutes prior to the start of the broadcast to ensure adequate time for any software download that may be necessary.

Financial Results
On a GAAP basis, for the three months ended September 30, 2021, the Company reported a net loss of $48.1 million, or $0.60 per basic and diluted share, compared to a net loss of $196.5 million reported for the same period of 2020, or $2.50 per basic and diluted share. On a non-GAAP basis, the net loss for the three months ended September 30, 2021 was $15.6 million, or $0.19 per basic and diluted share, compared to a net loss of $111.5 million, or $1.42 per basic and diluted share for the same period of 2020.

On a GAAP basis, for the nine months ended September 30, 2021, the Company reported a net loss of $296.8 million, or $3.72 per basic and diluted share, compared to a net loss of $364.8 million reported for the same period of 2020, or $4.70 per basic and diluted share. On a non-GAAP basis, the net loss for the nine months ended September 30, 2021 was $259.2 million, or $3.25 per basic and diluted share, compared to a net loss of $309.2 million, or $3.98 per basic and diluted share for the same period of 2020.

Revenues
For the three months ended September 30, 2021, the Company recorded total revenues of $189.4 million, compared to total revenues of $143.9 million for the same period of 2020, an increase of $45.5 million. For the nine months ended September 30, 2021, the Company recorded total revenues of $500.4 million, compared to total revenues of $395.0 million for the same period of 2020, an increase of $105.4 million.

For the three months ended September 30, 2021, the Company recorded net product revenues of $166.9 million, compared to net product revenues of $121.4 million for the same period of 2020, an increase of $45.5 million. For the nine months ended September 30, 2021, the Company recorded net product revenues of $433.7 million, compared to net product revenues of $333.2 million for the same period of 2020, an increase of $100.5 million. The increase primarily reflects the launch of AMONDYS 45 in the first quarter of 2021 and the continuing increase in demand for the Company’s other two products in the U.S.

For both the three months ended September 30, 2021 and 2020, the Company recognized $22.5 million of collaboration revenue. For the nine months ended September 30, 2021 and 2020, the Company recognized $66.8 million and $61.7 million of collaboration revenue, respectively. For all periods presented, collaboration revenue primarily relates to the F. Hoffman-La Roche Ltd. (Roche) collaboration arrangement.

Cost and Operating Expenses
Cost of sales (excluding amortization of in-licensed rights)
For the three months ended September 30, 2021, cost of sales (excluding amortization of in-licensed rights) was $23.4 million, compared to $15.0 million for the same period of 2020, an increase of $8.4 million. The increase in cost of sales is primarily due to increasing demand for the Company’s products. For the nine months ended September 30, 2021, cost of sales (excluding amortization of in-licensed rights) was $65.3 million, compared to $41.0 million for the same period of 2020, an increase of $24.3 million. The increase is primarily due to increasing demand for the Company’s products and the write-offs of certain batches of the Company’s products not meeting the Company’s quality specifications for the nine months ended September 30, 2021, with no similar activity during the same period of 2020.

Research and development
Research and development expenses were $139.1 million for the three months ended September 30, 2021, compared to $190.4 million for the same period of 2020, a decrease of $51.3 million. The decrease in research and development expenses primarily reflects the following:

$27.5 million decrease in manufacturing expenses primarily due to timing of production activity related to the Company’s gene therapy programs;
$10.9 million decrease in up-front and milestone expenses primarily due to $15.1 million of up-front payments as a result of the execution of certain research, option and license agreements during the third quarter of 2020, offset primarily by $4.5 million of similar activity during the third quarter of 2021;
$6.2 million decrease in clinical trial expenses primarily due to a ramp-down of enrollment for certain clinical trials as well as the timing of contract research organization activities;
$2.1 million decrease in collaboration cost sharing expenses with Genethon on its micro-dystrophin drug candidate and Lysogene S.A. on its MPS IIIA drug candidate;
$1.6 million decrease in compensation and other personnel expenses primarily due to changes in headcount;
$1.4 million increase in stock-based compensation expense primarily driven by changes in headcount and stock price;
$2.5 million increase in research and other expenses primarily driven by an increase in sponsored research with academic institutions during the three months ended September 30, 2021;
$2.8 million increase in pre-clinical expenses primarily due to an increase of toxicology studies in the Company’s PPMO platforms;
$3.8 million increase in facility- and technology-related expenses due to the Company’s continuing expansion efforts; and
$12.7 million increase in the offset to expense associated with a collaboration reimbursement from Roche primarily due to continuing development of the Company’s SRP-9001 micro-dystrophin gene therapy.
Research and development expenses were $573.9 million for the nine months ended September 30, 2021, compared to $515.1 million for the same period of 2020, an increase of $58.8 million. The increase in research and development expenses primarily reflects the following:

$16.2 million increase in manufacturing expenses primarily due to a continuing ramp-up of the Company’s gene therapy programs;
$15.4 million increase in research and other expenses primarily driven by an increase in sponsored research with academic institutions during the nine months ended September 30, 2021;
$13.6 million increase in clinical trial expenses primarily due to increased patient enrollment for the Company’s ESSENCE and MOMENTUM programs as well as certain start-up activities for the Company’s SRP-9001 micro-dystrophin program including for the Company’s EMBARK program;
$11.8 million increase in facility- and technology-related expenses primarily due to the Company’s continuing expansion efforts;
$10.5 million increase in pre-clinical expenses primarily due to an increase of toxicology studies in the Company’s PPMO platforms;
$5.0 million increase in stock-based compensation expense primarily due to changes in headcount and stock price;
$4.6 million increase in compensation and other personnel expenses primarily due to changes in headcount;
$3.5 million increase in up-front, milestone and other expenses primarily due to a $28.7 million increase of an accrued sublicense fee to Nationwide Children’s Hospital (Nationwide) and $11.5 million of expense incurred as a result of up-front payments and milestone achievements in certain research and license agreements during the nine months ended September 30, 2021, offset by $9.3 million of expense related to sublicense payments accrued to Nationwide and $27.1 million of up-front payments as a result of the execution of certain research and license agreements during the same period of 2020;
$3.4 million decrease in professional service expenses primarily due to a decrease in reliance on third-party research and development contractors; and
$18.7 million increase in the offset to expense associated with a collaboration reimbursement from Roche primarily due to continuing development of the Company’s SRP-9001 micro-dystrophin gene therapy.
Non-GAAP research and development expenses were $115.1 million and $159.9 million for the three months ended September 30, 2021 and 2020, respectively, a decrease of $44.8 million. Non-GAAP research and development expenses were $477.6 million and $434.5 million for the nine months ended September 30, 2021 and 2020, respectively, an increase of $43.1 million.

Selling, general and administration
Selling, general and administrative expenses were approximately $61.1 million for the three months ended September 30, 2021, compared to $75.4 million for the same period in 2020, a decrease of $14.3 million. The decrease in selling, general and administrative expenses primarily reflects the following:

$9.3 million decrease in professional service expenses primarily due to a decrease in reliance on third-party selling, general and administrative contractors;
$4.8 million decrease in compensation and other personnel expenses primarily due to a net decrease in headcount period over period;
$1.6 million decrease in stock-based compensation expense primarily due to changes in headcount and stock prices; and
$1.1 million increase in facility- and technology-related expenses primarily due to the Company’s continuing expansion efforts.
Selling, general and administrative expenses were approximately $204.6 million for the nine months ended September 30, 2021, compared to $231.8 million for the same period in 2020, a decrease of $27.2 million. The decrease in selling, general and administrative expenses primarily reflects the following:

$25.5 million decrease in professional service expenses primarily due to a decrease in reliance on third-party selling, general and administrative contractors, as well as a transaction fee for the Roche transaction incurred during the nine months ended September 30, 2020, with no similar activity incurred during the nine months ended September 30, 2021;
$4.2 million decrease in compensation and other personnel expenses primarily due to a net decrease in headcount period over period; and
$1.8 million increase in facility- and technology-related expenses primarily due to the Company’s continuing expansion efforts.
Non-GAAP selling, general and administrative expenses were $43.6 million and $57.2 million for the three months ended September 30, 2021 and 2020, respectively, a decrease of $13.6 million. Non-GAAP selling, general and administrative expenses were $149.2 million and $166.8 million for the nine months ended September 30, 2021 and 2020, respectively, a decrease of $17.6 million.

Settlement and license charges
In February 2021, the Company recognized a $10.0 million settlement charge related to contingent settlement payments to BioMarin Pharmaceutical, Inc. (BioMarin) as a result of the approval of AMONDYS 45 in the U.S. This was a result of a settlement and license agreement with BioMarin in July 2017. There was no such expense recognized during the same period of 2020.

Amortization of in-licensed rights
For each of the three months ended September 30, 2021 and 2020, the Company recorded amortization of in-licensed rights of approximately $0.2 million. For each of the nine months ended September 30, 2021 and 2020, the Company recorded amortization of in-licensed rights of approximately $0.5 million. This is related to the amortization of the in-licensed right assets recognized as a result of agreements the Company entered into with BioMarin and the University of Western Australia.

Gain (loss) on contingent consideration, net
The gain (loss) on contingent consideration, net, relates to the fair value adjustment of the Company’s contingent consideration derivative liability related to regulatory-related contingent payments to Myonexus Therapeutics, Inc. (Myonexus) selling shareholders as well as to two academic institutions under separate license agreements that meet the definition of a derivative. During the three and nine months ended September 30, 2021 and 2020, the Company recognized a $7.2 million net gain and $45.0 million net loss, respectively, to adjust the fair value of the contingent consideration.

Other expense, net
For the three months ended September 30, 2021 and 2020, other expense, net was $20.6 million and $14.3 million, respectively. For the nine months ended September 30, 2021 and 2020, other expense, net was $52.4 million and $34.2 million, respectively. The increases primarily reflect an increase in interest expense incurred on the Company’s term loan debt facilities due to an increase in the outstanding balance as well as an impairment loss related to a strategic investment, partially offset by a reduction of interest expense incurred on the Company’s convertible debt related to the adoption of ASU 2020-06.

Gain from sale of Priority Review Voucher
In February 2021, the Company entered into an agreement to sell the rare pediatric disease Priority Review Voucher (PRV) it received from the FDA in connection with the approval of AMONDYS 45. Following the termination of the applicable waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976, as amended, in April 2021, the Company completed its sale of the PRV and received proceeds of $102.0 million, with no commission costs, which was recorded as a gain from sale of the PRV as it did not have a carrying value at the time of the sale.

In February 2020, the Company entered into an agreement to sell the PRV it received from the FDA in connection with the approval of VYONDYS 53. In March 2020, the Company completed its sale of the PRV and received proceeds of $108.1 million, net of commission, which was recorded as a gain from sale of the PRV as it did not have a carrying value at the time of the sale.

Cash, Cash Equivalents, Investments and Restricted Cash and Investments
The Company had approximately $1.6 billion in cash, cash equivalents and investments as of September 30, 2021, compared to $1.9 billion as of December 31, 2020. The decrease is primarily driven by cash used to fund the Company’s ongoing operations during 2021.

Use of Non-GAAP Measures
In addition to the GAAP financial measures set forth in this press release, the Company has included certain non-GAAP measurements. The non-GAAP loss is defined by the Company as GAAP net loss excluding interest expense, net, income tax (benefit) expense, depreciation and amortization expense, stock-based compensation expense and other items. Non-GAAP research and development expenses are defined by the Company as GAAP research and development expenses excluding depreciation and amortization expense, stock-based compensation expense and other items. Non-GAAP selling, general and administrative expenses are defined by the Company as GAAP selling, general and administrative expenses excluding depreciation and amortization expense, stock-based compensation expense and other items.

1. Interest, tax, depreciation and amortization
Interest expense, net amounts can vary substantially from period to period due to changes in cash and debt balances and interest rates driven by market conditions outside of the Company’s operations. Tax amounts can vary substantially from period to period due to tax adjustments that are not directly related to underlying operating performance. Depreciation expense can vary substantially from period to period as the purchases of property and equipment may vary significantly from period to period and without any direct correlation to the Company’s operating performance. Amortization expense primarily associated with in-licensed rights as well as patent costs are amortized over a period of several years after acquisition or patent application or renewal and generally cannot be changed or influenced by management.

2. Stock-based compensation expenses
Stock-based compensation expenses represent non-cash charges related to equity awards granted by the Company. Although these are recurring charges to operations, the Company believes the measurement of these amounts can vary substantially from period to period and depend significantly on factors that are not a direct consequence of operating performance that is within the Company’s control. Therefore, the Company believes that excluding these charges facilitates comparisons of the Company’s operational performance in different periods.

3. Other items
The Company evaluates other items of expense and income on an individual basis. It takes into consideration quantitative and qualitative characteristics of each item, including (a) nature, (b) whether the items relate to the Company’s ongoing business operations, and (c) whether the Company expects the items to continue on a regular basis. These other items include collaboration revenue and transaction cost related to the Roche transaction, up-front and milestone payments, gain from sale of PRV, settlement and license charges, impairment of equity investment and net gain (loss) on contingent consideration.

The Company excludes collaboration revenue and transaction cost associated with the Roche transaction from its non-GAAP results. While collaboration revenue is recurring, as the Company’s ordinary activities do not include contracting with third parties to provide them with research and development services, collaboration revenue is treated as a non-GAAP adjustment item. Additionally, the transaction fee related to the Roche transaction is non-recurring and is excluded from its non-GAAP results. However, the Company does not exclude reimbursement of costs by Roche from its non-GAAP results.

The Company excludes up-front and milestone payments associated with its license and collaboration agreements from its non-GAAP results and research and development expenses because the Company does not consider them to be normal operating expenses due to their nature, variability of amounts, and lack of predictability as to occurrence and/or timing. Up-front payments are made at the commencement of a collaborative relationship or a license agreement anticipated to continue for a multi-year period and provide the Company with intellectual property rights, option rights and other rights with respect to particular programs. Milestone payments are made when certain development, regulatory and sales milestone events are achieved. The variability of amounts and lack of predictability of collaboration- and license-related up-front and milestone payment makes the identification of trends in the Company’s ongoing research and development activities more difficult.

The sale of the PRVs obtained as a result of the FDA approval of VYONDYS 53 and AMONDYS 45 in December 2019 and February 2021, respectively, are non-recurring events and excluded from the Company’s non-GAAP results.

The Company excludes settlement and license charges from its non-GAAP results because the Company does not consider them to be normal operating expenses due to their nature, variability of amounts, and lack of predictability as to occurrence and/or timing.

The Company excludes from its non-GAAP results the impairment of any equity investments as it is a non-cash item and is not considered to be a normal operating expense due to the variability of amount and lack of predictability as to the occurrence and/or timing of such impairments.

The Company excludes from its non-GAAP results the net gain (loss) on contingent consideration related to regulatory-related contingent payments meeting the definition of a derivative to Myonexus selling shareholders as well as to two academic institutions under separate license agreements as it is a non-cash item and is not considered to be normal operating expenses due to its variability of amounts and lack of predictability as to occurrence and/or timing.
The Company uses these non-GAAP measures as key performance measures for the purpose of evaluating operational performance and cash requirements internally. The Company also believes these non-GAAP measures increase comparability of period-to-period results and are useful to investors as they provide a similar basis for evaluating the Company’s performance as is applied by management. These non-GAAP measures are not intended to be considered in isolation or to replace the presentation of the Company’s financial results in accordance with GAAP. Use of the terms non-GAAP research and development expenses, non-GAAP selling, general and administrative expenses, non-GAAP other income and loss adjustments, non-GAAP income tax (benefit) expense, non-GAAP net loss, and non-GAAP basic and diluted net loss per share may differ from similar measures reported by other companies, which may limit comparability, and are not based on any comprehensive set of accounting rules or principles. All relevant non-GAAP measures are reconciled from their respective GAAP measures in the attached table "Reconciliation of GAAP Financial Measures to Non-GAAP Financial Measures."

About EXONDYS 51
EXONDYS 51 (eteplirsen) uses Sarepta’s proprietary phosphorodiamidate morpholino oligomer (PMO) chemistry and exon-skipping technology to bind to exon 51 of dystrophin pre-mRNA, resulting in exclusion, or "skipping", of this exon during mRNA processing in patients with genetic mutations that are amenable to exon 51 skipping. Exon skipping is intended to allow for production of an internally truncated dystrophin protein.

EXONDYS 51 is indicated for the treatment of Duchenne muscular dystrophy in patients who have a confirmed mutation of the dystrophin gene that is amenable to exon 51 skipping.

This indication is approved under accelerated approval based on an increase in dystrophin production in skeletal muscle observed in some patients treated with EXONDYS 51. Continued approval may be contingent upon verification of a clinical benefit in confirmatory trials.

EXONDYS 51 has met the full statutory standards for safety and effectiveness and as such is not considered investigational or experimental.

Important Safety Information About EXONDYS 51
Hypersensitivity reactions, including rash and urticaria, pyrexia, flushing, cough, dyspnea, bronchospasm, and hypotension, have occurred in patients who were treated with EXONDYS 51. If a hypersensitivity reaction occurs, institute appropriate medical treatment and consider slowing the infusion or interrupting the EXONDYS 51 therapy.

Adverse reactions in Duchenne patients (N=8) treated with EXONDYS 51 30 mg or 50 mg/kg/week by intravenous (IV) infusion with an incidence of at least 25% more than placebo (N=4) (Study 1, 24 weeks) were (EXONDYS 51, placebo): balance disorder (38%, 0%), vomiting (38%, 0%) and contact dermatitis (25%, 0%). The most common adverse reactions were balance disorder and vomiting. Because of the small numbers of patients, these represent crude frequencies that may not reflect the frequencies observed in practice. The 50 mg/kg once weekly dosing regimen of EXONDYS 51 is not recommended.

In the 88 patients who received ≥30 mg/kg/week of EXONDYS 51 for up to 208 weeks in clinical studies, the following events were reported in ≥10% of patients and occurred more frequently than on the same dose in Study 1: vomiting, contusion, excoriation, arthralgia, rash, catheter site pain, and upper respiratory tract infection.

For further information, please see the full Prescribing Information.

About VYONDYS 53
VYONDYS 53 (golodirsen) uses Sarepta’s proprietary phosphorodiamidate morpholino oligomer (PMO) chemistry and exon-skipping technology to bind to exon 53 of dystrophin pre-mRNA, resulting in exclusion, or "skipping," of this exon during mRNA processing in patients with genetic mutations that are amenable to exon 53 skipping. Exon skipping is intended to allow for production of an internally truncated dystrophin protein.

VYONDYS 53 is indicated for the treatment of Duchenne muscular dystrophy in patients who have a confirmed mutation of the dystrophin gene that is amenable to exon 53 skipping.

This indication is approved under accelerated approval based on an increase in dystrophin production in skeletal muscle observed in patients treated with VYONDYS 53. Continued approval may be contingent upon verification of a clinical benefit in confirmatory trials.

VYONDYS 53 has met the full statutory standards for safety and effectiveness and as such is not considered investigational or experimental.

Important Safety Information for VYONDYS 53
Hypersensitivity reactions, including rash, pyrexia, pruritus, urticaria, dermatitis, and skin exfoliation have occurred in VYONDYS 53-treated patients, some requiring treatment. If a hypersensitivity reaction occurs, institute appropriate medical treatment and consider slowing the infusion or interrupting the VYONDYS 53 therapy.

Kidney toxicity was observed in animals who received golodirsen. Although kidney toxicity was not observed in the clinical studies with VYONDYS 53, the clinical experience with VYONDYS 53 is limited, and kidney toxicity, including potentially fatal glomerulonephritis, has been observed after administration of some antisense oligonucleotides. Kidney function should be monitored in patients taking VYONDYS 53. Because of the effect of reduced skeletal muscle mass on creatinine measurements, creatinine may not be a reliable measure of kidney function in Duchenne patients. Serum cystatin C, urine dipstick, and urine protein-to-creatinine ratio should be measured before starting VYONDYS 53. Consider also measuring glomerular filtration rate using an exogenous filtration marker before starting VYONDYS 53. During treatment, monitor urine dipstick every month, and serum cystatin C and urine protein-to-creatinine ratio every three months. Only urine expected to be free of excreted VYONDYS 53 should be used for monitoring of urine protein. Urine obtained on the day of VYONDYS 53 infusion prior to the infusion, or urine obtained at least 48 hours after the most recent infusion, may be used. Alternatively, use a laboratory test that does not use the reagent pyrogallol red, as this reagent has the potential to cross react with any VYONDYS 53 that is excreted in the urine and thus lead to a false positive result for urine protein.

If a persistent increase in serum cystatin C or proteinuria is detected, refer to a pediatric nephrologist for further evaluation.

Adverse reactions observed in at least 20% of treated patients and greater than placebo were (VYONDYS 53, placebo): headache (41%, 10%), pyrexia (41%, 14%), fall (29%, 19%), abdominal pain (27%, 10%), nasopharyngitis (27%, 14%), cough (27%, 19%), vomiting (27%, 19%), and nausea (20%, 10%).

Other adverse reactions that occurred at a frequency greater than 5% of VYONDYS 53-treated patients and at a greater frequency than placebo were: administration site pain, back pain, pain, diarrhea, dizziness, ligament sprain, contusion, influenza, oropharyngeal pain, rhinitis, skin abrasion, ear infection, seasonal allergy, tachycardia, catheter site related reaction, constipation, and fracture.

For further information, please see the full Prescribing Information.

About AMONDYS 45
AMONDYS 45 (casimersen) uses Sarepta’s proprietary phosphorodiamidate morpholino oligomer (PMO) chemistry and exon-skipping technology to bind to exon 45 of dystrophin pre-mRNA, resulting in exclusion, or "skipping," of this exon during mRNA processing in patients with genetic mutations that are amenable to exon 45 skipping. Exon skipping is intended to allow for production of an internally truncated dystrophin protein.

AMONDYS 45 is indicated for the treatment of Duchenne muscular dystrophy in patients who have a confirmed mutation of the dystrophin gene that is amenable to exon 45 skipping.

This indication is approved under accelerated approval based on an increase in dystrophin production in skeletal muscle observed in patients treated with AMONDYS 45. Continued approval may be contingent upon verification of a clinical benefit in confirmatory trials.

AMONDYS 45 has met the full statutory standards for safety and effectiveness and as such is not considered investigational or experimental.

Important Safety Information for AMONDYS 45
Kidney toxicity was observed in animals who received casimersen. Although kidney toxicity was not observed in the clinical studies with AMONDYS 45, kidney toxicity, including potentially fatal glomerulonephritis, has been observed after administration of some antisense oligonucleotides. Kidney function should be monitored in patients taking AMONDYS 45. Because of the effect of reduced skeletal muscle mass on creatinine measurements, creatinine may not be a reliable measure of kidney function in Duchenne patients. Serum cystatin C, urine dipstick, and urine protein-to-creatinine ratio should be measured before starting AMONDYS 45. Consider also measuring glomerular filtration rate using an exogenous filtration marker before starting AMONDYS 45. During treatment, monitor urine dipstick every month, and serum cystatin C and urine protein-to-creatinine ratio (UPCR) every three months. Only urine expected to be free of excreted AMONDYS 45 should be used for monitoring of urine protein. Urine obtained on the day of AMONDYS 45 infusion prior to the infusion, or urine obtained at least 48 hours after the most recent infusion, may be used. Alternatively, use a laboratory test that does not use the reagent pyrogallol red, as this reagent has the potential to cross react with any AMONDYS 45 that is excreted in the urine and thus lead to a false positive result for urine protein.

If a persistent increase in serum cystatin C or proteinuria is detected, refer to a pediatric nephrologist for further evaluation.

Adverse reactions observed in at least 20% of patients treated with AMONDYS 45 and at least 5% more frequently than in the placebo group were (AMONDYS 45, placebo): upper respiratory tract infections (65%, 55%), cough (33%, 26%), pyrexia (33%, 23%), headache (32%, 19%), arthralgia (21%, 10%), and oropharyngeal pain (21%, 7%).

Other adverse reactions that occurred in at least 10% of patients treated with AMONDYS 45 and at least 5% more frequently in the placebo group, were: ear pain, nausea, ear infection, post-traumatic pain, and dizziness and light-headedness.

For further information, please see the full Prescribing Information.

On November 4, 2021 Onconova Therapeutics, Inc. (NASDAQ: ONTX), a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer, reported that the Company intends to release its third quarter 2021 financial results on Thursday, November 11, 2021 (Press release, Onconova, NOV 4, 2021, View Source [SID1234594492]). Management plans to host a conference call and live webcast at 4:30 p.m. ET on that day to discuss these results and provide an update on its pipeline programs.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Conference Call and Webcast Information

Interested parties who wish to participate in the conference call may do so by dialing (855) 428-5741 for domestic and (210) 229-8823 for international callers and using conference ID 5367655.

Those interested in listening to the conference call via the internet may do so by visiting the investors and media page on the company’s website at www.onconova.com and clicking on the webcast link. In addition to the live webcast, a replay will be available on the Onconova website for 90 days following the call.

On November 4, 2021 Precigen, Inc. (Nasdaq: PGEN), a biopharmaceutical company specializing in the development of innovative gene and cell therapies to improve the lives of patients, reported a topline summary of the presentations planned for today’s 2021 R&D Day virtual event, which begins at 11:00 AM ET (Press release, Precigen, NOV 4, 2021, View Source [SID1234594509]). Participants may register and access the live webcast through Precigen’s investor relations website in the Events & Presentations section.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Today’s event will showcase clinical progress for Precigen’s UltraCAR-T platform, including PRGN-3005 UltraCAR-T, PRGN-3006 UltraCAR-T, PRGN-3007 UltraCAR-T and the AdenoVerse immunotherapy platform, including PRGN-2009 off-the-shelf (OTS) AdenoVerse Immunotherapy, and PRGN-2012 OTS AdenoVerse Immunotherapy. Presentations will be made by Precigen executives and clinical trial investigators, including:

Helen Sabzevari, PhD, President and CEO of Precigen;
Mary L. (Nora) Disis, MD, University of Washington (UW) Professor of Medicine, Director of UW Center for Translational Medicine, Professor in the Clinical Research Division at the Fred Hutchinson Cancer Research Center and a lead investigator for the PRGN-3005 clinical trial;
David Sallman, MD, Assistant Member in the Department of Malignant Hematology at the H. Lee Moffitt Cancer Center & Research Institute and a lead investigator for the PRGN-3006 clinical trial;
James L. Gulley, MD, PhD, FACP, Branch Chief and Director of the Medical Oncology Service at the National Institutes of Health (NIH) and a lead investigator for the PRGN-2009 clinical trial; and
Clint T. Allen, MD, Principal Investigator with the Section on Translational Tumor Immunology at the NIH and a lead investigator for the PRGN-2012 clinical trial.
"Today’s R&D Day highlights the most significant clinical data presented for the UltraCAR-T and AdenoVerse platforms to date," said Helen Sabzevari, PhD, President and CEO of Precigen, "and we are highly encouraged by the initial results we are seeing across assets in both platforms. With UltraCAR-T, initial data for PRGN-3005 and PRGN-3006 continue to demonstrate favorable safety profiles, dose-dependent expansion, and durable persistence. The very encouraging clinical responses in relapsed or refractory AML patients treated with PRGN-3006 at the two lowest dose levels in the lymphodepletion cohort, which are administered at significantly lower doses than competing approaches, highlight the potential of the UltraCAR-T platform. Our AdenoVerse immunotherapy platform is equally impressive with initial data for PRGN-2009 and PRGN-2012 showing antigen-specific immune responses, low neutralizing antibody responses, and favorable safety profiles highlighting the potential for repeat administrations. Preliminary data for PRGN-2009 show encouraging objective responses and suggest an attractive opportunity for potential combination of PRGN-2009 with checkpoint inhibitors in multiple HPV-associated cancers. Finally, preliminary data for PRGN-2012 show encouraging clinical responses in RRP patients, including a reduction in surgical interventions following PRGN-2012 treatment. We are on track to pursue potentially registrational trials for therapeutic candidates in both the UltraCAR-T and AdenoVerse platforms upon dose confirmation and expansion."

PRGN-3006 UltraCAR-T

Overview: PRGN-3006 is an investigational multigenic, autologous chimeric antigen receptor T cell (CAR-T) therapy engineered to simultaneously express a chimeric antigen receptor (CAR) specifically targeting CD33, membrane bound IL-15 (mbIL15), and a kill switch. PRGN-3006 UltraCAR-T is under evaluation in a Phase 1/1b clinical trial for the treatment of patients with r/r AML or higher-risk myelodysplastic syndromes (MDS). Trial subjects receive the PRGN-3006 infusion either without prior lymphodepletion (Cohort 1) or following lymphodepleting chemotherapy (Cohort 2). PRGN-3006 UltraCAR-T has been granted Orphan Drug Designation in patients with AML by the US Food and Drug Administration (US FDA).
Enrollment: Enrollment in Dose Level 4 of the non-lymphodepletion cohort and Dose Level 3 of the lymphodepletion cohort of the Phase 1 dose escalation trial is ongoing concurrently.
Dosing: As of the July 25, 2021 data cut-off, 15 r/r AML patients were treated in the non-lymphodepletion cohort (N=9) and the lymphodepletion cohort (N=6). Patients were heavily pre-treated with a median of 4 (range: 1 to 6) and 3 (range: 1 to 7) prior regimens in the non-lymphodepletion and the lymphodepletion cohorts, respectively. Additionally, 33% and 50% of the patients had failed prior allogeneic hematopoietic stem cell transplant (allo-HSCT) in the non-lymphodepletion and the lymphodepletion cohorts, respectively. Patients received a single PRGN-3006 administration at one of the following dose levels:

Non-lymphodepletion Cohort (Cohort 1)

Dose Level (DL)

Subjects

Dose Range

(UltraCAR-T Cells/kg)

Total UltraCAR-T Dose
Administered

DL1

N=3

>3×104 to ≤1×105

1.8 to 7.1 x106 cells

DL2

N=3

>1×105 to ≤ 3×105

24 to 29 x106 cells

DL3

N=3

>3×105 to ≤ 1×106

34 to 50 x106 cells

Lymphodepletion Cohort (Cohort 2)

Dose Level (DL)

Subjects

Dose Range

(UltraCAR-T Cells/kg)

Total UltraCAR-T Dose
Administered

DL1

N=3

>3×104 to ≤1×105

4.4 to 10 x106 cells

DL2

N=3

>1×105 to ≤ 3×105

18 to 28 x106 cells

Safety data: Data from the first three dose levels in Cohort 1 (non-lymphodepletion) and the first two dose levels in Cohort 2 (lymphodepletion) show that PRGN-3006 was well-tolerated with no dose-limiting toxicities (DLTs) and no neurotoxicity. Only one transient Grade 3 cytokine release syndrome (CRS) was reported (DL1, Cohort 1), which resolved in less than 24 hours with tocilizumab and dexamethasone. Remaining cases of CRS were Grade 1 or 2 that either required no specific intervention or resolved following standard CRS management.
Clinical activity: Dose-dependent expansion and persistence in both the non-lymphodepletion and the lymphodepletion cohorts was observed.
An ORR of 50% (3 out of 6) was reported in the lymphodepletion cohort (Cohort 2) in patients treated at the two lowest dose levels. This included an ORR of 33% (1 out of 3) at Dose Level 1 and 67% (2 out of 3) at Dose Level 2.
Objective responses included one partial response (PR) in a patient with extramedullary AML, one complete response with incomplete hematologic recovery (CRi) which was bridged to allo-HSCT, and one complete response with hematologic recovery (CRh).
Upcoming presentation: An abstract for the PRGN-3006 Phase 1 trial (Abstract# 825) titled, "Phase 1/1b Safety Study of PRGN-3006 UltraCAR-T in Patients with Relapsed or Refractory CD33-Positive Acute Myeloid Leukemia and Higher Risk Myelodysplastic Syndromes," was selected for oral presentation at the 63rd ASH (Free ASH Whitepaper) Annual Meeting and Exposition on December 13, 2021 at 5:00 PM ET.
PRGN-3005 UltraCAR-T

Overview: PRGN-3005 UltraCAR-T is an investigational multigenic, autologous CAR-T cell therapy engineered to express a CAR specifically targeting the unshed portion of MUC16, which is highly expressed on ovarian tumors with limited normal tissue expression, mbIL15, and a kill switch. PRGN-3005 UltraCAR-T is under evaluation in a Phase 1/1b clinical trial for the treatment of patients with advanced, recurrent platinum resistant ovarian cancer. Trial subjects receive PRGN-3005 either via intraperitoneal (IP) (Arm A) or intravenous (IV) (Arm B) infusion.
Enrollment: Doses are currently being administered without lymphodepletion. Dose escalation in the IP arm and IV arm is ongoing concurrently.
Dosing: Ten heavily pretreated, advanced, platinum resistant ovarian cancer patients with aggressive disease were treated with a single IP infusion of PRGN-3005 without prior lymphodepletion at one of the following dose levels:

Dose Level (DL)

Subjects

Dose Range

(UltraCAR-T Cells/kg)

Total UltraCAR-T Dose
Administered

DL1

N=3

>3×104 to ≤1×105

6 to 7.6 x106 cells

DL2

N=3

>1×105 to ≤ 3×105

12 to 21 x106 cells

DL3

N=4

>3×105 to ≤ 5×106

33 to 321 x106 cells

Manufacturing: Precigen’s UltraPorator system has enabled escalation to higher doses, as evidenced by the successful infusion of greater than 320 million UltraCAR-T cells, through the decentralized UltraCAR-T manufacturing process.
Safety data: New data continue to show a favorable safety profile with no DLTs, no neurotoxicity, and no CRS reported.
Clinical activity: Data show dose-dependent expansion and persistence in the peripheral blood for more than 3 months after PRGN-3005 treatment without lymphodepletion, and clinical activity as evidenced by a decrease or stabilization of total target tumor burden at the first restaging in a majority of patients.
Next steps: Complete dose escalation in the IP and IV arms and, subsequently, incorporate lymphodepletion prior to PRGN-3005 infusion, which was cleared by the US FDA. Additionally, based on the favorable safety profile, the potential for repeat dosing is being evaluated.
PRGN-3007 Next Generation UltraCAR-T with Intrinsic PD-1 Inhibition

Overview: PRGN-3007, based on the next generation of UltraCAR-T platform, is an investigational multigenic, autologous CAR-T cell therapy engineered to simultaneously express a CAR targeting receptor tyrosine kinase-like orphan receptor 1 (ROR1), mbIL15, a kill switch, and a novel mechanism for the intrinsic blockade of PD-1 gene expression. ROR1 is aberrantly expressed in multiple hematological and solid tumors with minimal expression in healthy adult tissues.
Trial design: As recently announced, the US FDA cleared the investigational new drug (IND) application to initiate a Phase 1/1b open-label trial designed to evaluate the safety and efficacy of PRGN-3007 in patients with advanced ROR1+ hematological (Arm 1) and solid (Arm 2) tumors. The target patient population for Arm 1 includes r/r chronic lymphocytic leukemia (CLL), r/r mantle cell leukemia (MCL), r/r acute lymphoblastic leukemia (ALL), and r/r diffuse large B-cell lymphoma (DLBCL). The target patient population for Arm 2 includes locally advanced unresectable or metastatic histologically confirmed triple negative breast cancer (TNBC). The trial will enroll in two parts: an initial 3+3 dose escalation in each arm followed by a dose expansion at the maximum tolerated dose. Arm 1 and Arm 2 will enroll in parallel.
Preclinical data: An abstract highlighting PRGN-3007 preclinical data (Abstract# 1694) titled, "Preclinical evaluation of PRGN-3007, a non-viral, multigenic, autologous ROR1 UltraCAR-T cell therapy with novel mechanism of intrinsic PD-1 blockade for treatment of hematological and solid cancers," will be presented as a poster presentation at the 63rd ASH (Free ASH Whitepaper) Annual Meeting and Exposition.
PRGN-2012 OTS AdenoVerse Immunotherapy

Overview: PRGN-2012 is an investigational OTS AdenoVerse immunotherapy designed to elicit immune responses directed against cells infected with HPV 6 or HPV 11 for treatment of recurrent respiratory papillomatosis (RRP). PRGN-2012 is currently under evaluation in a Phase 1 clinical trial under a Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI). The Phase 1 trial is designed to follow 3+3 dose escalation of PRGN-2012 as an adjuvant immunotherapy following standard-of-care surgical removal of visible papillomas in adult patients with RRP. PRGN-2012 has been granted Orphan Drug Designation in patients with RRP by the US FDA.
Enrollment: Enrollment in the Phase 1 dose escalation portion of the trial is complete and enrollment in the expansion cohort is ongoing.
Dosing: Six patients have been enrolled in the Phase 1 dose escalation arm at one of the following dose levels with patients receiving four PRGN-2012 administrations (on days 1, 15, 43 and 85) via subcutaneous injection:
Dose Level 1: 1 x 1011 viral particles (vp)/dose; N=3
Dose Level 2: 5 x 1011 vp/dose; N=3
Additionally, 8 patients have been enrolled in the Phase 1 dose expansion arm to receive four PRGN-2012 administrations (on days 1, 15, 43 and 85) at 5 x 1011 vp/dose via subcutaneous injection.
Baseline patient characteristics (N=14) included an average of 51 lifetime surgeries (range: 9 to > 800), and an average of 5.5 surgeries (range: 2 to 9) in the last 2 months before enrolling in the trial.
Safety data: Repeated administrations of PRGN-2012 were well-tolerated with no DLTs and no treatment-related adverse events greater than Grade 2. The lack of a significant neutralizing antibody response over time with subsequent additional vaccinations highlights the ability to deliver repeated administrations of PRGN-2012, a differentiating feature of the AdenoVerse platform.
Clinical activity: Preliminary data from three RRP patient case studies demonstrate very encouraging clinical activity of PRGN-2012 with reduction or elimination in the need for surgical interventions at the most recent follow-up, up to 12 weeks after PRGN-2012 treatment, compared to the recent history of surgical interventions for these patients before enrolling in the trial.
PRGN-2009 OTS AdenoVerse Immunotherapy

Overview: PRGN-2009 is an OTS investigational immunotherapy utilizing the AdenoVerse platform that has been designed to activate the immune system to recognize and target HPV-positive solid tumors. PRGN-2009 is currently under evaluation in a Phase 1/2 clinical trial under a CRADA with the NCI. The Phase 1 trial is evaluating safety and response of PRGN-2009 as monotherapy (Arm A) and in combination with bintrafusp alfa (Arm B) in previously treated patients with recurrent or metastatic HPV-associated cancers.
Enrollment: Enrollment in the Phase 1 monotherapy dose escalation arm is complete and enrollment in the Phase 1 combination arm is ongoing. In addition, enrollment in the monotherapy arm of the Phase 2 trial, which evaluates PRGN-2009 as a neoadjuvant therapy for newly diagnosed oropharyngeal or sinonasal squamous cell cancer patients (OPSCC) is ongoing.
Dosing: Six patients (all with prior anti-PD-1/PD-L1 treatment) have been treated in the Phase 1 monotherapy dose escalation arm at one of the following dose levels with patients receiving three PRGN-2009 administrations (on days 1, 15 and 29), followed by PRGN-2009 administration once every 4 weeks for up to 1 year:
Dose Level 1: 1 x 1011 vp/dose; N=3
Dose Level 2: 5 x 1011 vp/dose; N=3
Additionally, 6 patients (all with prior anti-PD-1/PD-L1 treatment) were treated in the Phase 1 combination arm with patients receiving three PRGN-2009 administrations (5 x 1011 vp/dose on days 1, 15 and 29) in combination with bintrafusp alfa (1200 mg) once every 2 weeks, followed by PRGN-2009 administration once every 4 weeks in combination with bintrafusp alfa administrations once every 2 weeks for up to 1 year. Five patients with at least one post-treatment scan were evaluable for disease response.
Safety data: Phase 1 data show that repeated administrations of PRGN-2009 demonstrated a favorable safety profile as monotherapy and in combination therapy with no DLTs. The lack of a significant neutralizing antibody response over time with subsequent additional vaccinations highlights the ability to deliver repeated administrations of PRGN-2009.
Clinical activity: Patient case studies show encouraging increases in the HPV16 and/or HPV18-specific immune response with repeated administrations of PRGN-2009.
In the Phase 1 monotherapy arm, a DCR of 50% (3 out of 6 with stable disease (SD)) at the first restaging was observed. This includes a patient with durable (>1 year) SD who has received 16 PRGN-2009 monotherapy administrations.
In the Phase 1 combination therapy arm, an ORR of 40% (2 out of 5) per RECIST v1.1 was observed. Objective responses included one ongoing CR at approximately 6 months after treatment initiation and one ongoing PR at approximately 7 months after treatment initiation. Additionally, a DCR of 60% (3 out of 5) at first restaging was observed.
Precigen: Advancing Medicine with Precision
Precigen (Nasdaq: PGEN) is a dedicated discovery and clinical stage biopharmaceutical company advancing the next generation of gene and cell therapies using precision technology to target the most urgent and intractable diseases in our core therapeutic areas of immuno-oncology, autoimmune disorders, and infectious diseases. Our technologies enable us to find innovative solutions for affordable biotherapeutics in a controlled manner. Precigen operates as an innovation engine progressing a preclinical and clinical pipeline of well-differentiated unique therapies toward clinical proof-of-concept and commercialization. For more information about Precigen, visit www.precigen.com or follow us on Twitter @Precigen and LinkedIn.

UltraCAR-T
UltraCAR-T is a multigenic autologous CAR-T platform that utilizes Precigen’s advanced non-viral Sleeping Beauty system to simultaneously express an antigen-specific CAR to specifically target tumor cells, mbIL15 for enhanced in vivo expansion and persistence, and a kill switch to conditionally eliminate CAR-T cells for a potentially improved safety profile. Precigen has advanced the UltraCAR-T platform to address the inhibitory tumor microenvironment by incorporating a novel mechanism for intrinsic checkpoint blockade without the need for complex and expensive gene editing techniques. UltraCAR-T investigational therapies are manufactured via Precigen’s overnight manufacturing process using the proprietary UltraPorator electroporation system at the medical center and administered to patients only one day following gene transfer. The overnight UltraCAR-T manufacturing process does not use viral vectors and does not require ex vivo activation and expansion of T cells, potentially addressing major limitations of current T cell therapies.

AdenoVerse Immunotherapy
Precigen’s AdenoVerse immunotherapy platform utilizes a library of proprietary adenovectors for the efficient gene delivery of therapeutic effectors, immunomodulators, and vaccine antigens designed to modulate the immune system. Precigen’s gorilla adenovectors, part of the AdenoVerse library, have potentially superior performance characteristics as compared to current competition. AdenoVerse immunotherapies have been shown to generate high-level and durable antigen-specific neutralizing antibodies and effector T cell immune responses as well as an ability to boost these antibody and T cell responses via repeat administration. Superior performance characteristics and high yield manufacturing of AdenoVerse vectors combined with UltraVector technology allows Precigen to engineer cutting-edge investigational gene therapies to treat complex diseases.

UltraPorator
The UltraPorator system is an exclusive device and proprietary software solution for the scale-up of rapid and cost-effective manufacturing of UltraCAR-T therapies and potentially represents a major advancement over current electroporation devices by significantly reducing the processing time and contamination risk. The UltraPorator device is a high-throughput, semi-closed electroporation system for modifying T cells using Precigen’s proprietary non-viral gene transfer technology. UltraPorator is being utilized for clinical manufacturing of Precigen’s investigational UltraCAR-T therapies in compliance with current good manufacturing practices.

Trademarks
Precigen, UltraCAR-T, AdenoVerse, UltraVector, UltraPorator and Advancing Medicine with Precision are trademarks of Precigen and/or its affiliates. Other names may be trademarks of their respective owners.