On November 3, 2022 Exelixis, Inc. (Nasdaq: EXEL) and Catalent, Inc. (NYSE: CTLT) reported a new license agreement under which Catalent’s Redwood Bioscience subsidiary will grant Exelixis an exclusive license to three target programs with lead antibody and/or ADC candidates (Press release, Exelixis, NOV 3, 2022, View Source [SID1234623013]). The ADC candidates have been developed using Catalent’s proprietary SMARTag technology, and each of the licensed antibodies has potential for development as an ADC or other biologic therapy using a variety of technologies to which Exelixis has access through its partner network. In September 2020, Exelixis and Catalent entered into a separate agreement under which Catalent is applying its SMARTag bioconjugation platform to build ADCs using monoclonal antibodies from Exelixis’ growing preclinical pipeline.

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Under the terms of the new agreement, Exelixis will make an upfront payment to Catalent of $30 million in exchange for rights to the three biologics programs. Exelixis will fund the development work conducted by Catalent until development candidate selection is complete, after which Exelixis will assume responsibility for conducting preclinical, clinical, and commercial activities. Catalent will be eligible for development and sales milestone payments, as well as sales-based royalties.

"Exelixis is committed to building a robust biologics pipeline, and this agreement expands our portfolio to include three highly promising targets with broad potential in multiple solid tumor indications, including bladder, breast, lung, ovarian, pancreatic, and other cancers," said Peter Lamb, Ph.D., Executive Vice President, Scientific Strategy and Chief Scientific Officer, Exelixis. "We believe that the antibodies, ADCs and data Catalent has generated to date will enable rapid advancement of these programs, enabling an acceleration of our in-house biotherapeutics pipeline. We are excited for this new opportunity to continue our work together to advance additional programs that have the potential to provide patients with new therapeutic options."

"Catalent Biologics is a leader in applying precision protein engineering and novel chemistries to develop optimized therapeutics," said Mike Riley, President, Division Head for BioProduct Delivery, Catalent Biologics. "Our versatile SMARTag platform and growing portfolio of preclinical ADCs against promising targets create multiple opportunities for Catalent to partner with leading biopharmaceutical companies, such as Exelixis. We expect the new license agreement with Exelixis will yield innovative and differentiated therapies with the potential to improve care and outcomes for cancer patients."

The SMARTag technology platform was developed by Redwood Bioscience based on discoveries in the lab of Carolyn Bertozzi, recent winner of the Nobel Prize in Chemistry and Chair of Redwood’s scientific advisory board. The platform provides optimized site-specific protein-modification, as well as linker and payload technologies for ADCs and other bioconjugates. The SMARTag platform overcomes the limitations associated with traditional protein chemistries that produce heterogeneous products with variable conjugate potency, toxicity, and stability, and enables the development of ADCs with a wider therapeutic window and improved manufacturability.

On November 3, 2022 BeiGene, (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global biotechnology company, reported clinical and real-world data accepted at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, scheduled for December 10-14, 2022, in New Orleans (Press release, BeiGene, NOV 3, 2022, View Source [SID1234623012]). BeiGene is focused on developing innovative and affordable oncology medicines to improve treatment outcomes and access for patients worldwide.

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Key presentations

Phase 1 trial results demonstrating proof of concept for BGB-11417, a novel B-cell lymphoma 2 (Bcl-2) inhibitor in chronic lymphocytic leukemia/small lymphocytic leukemia;
Long-term efficacy and safety data from the MAGNOLIA trial of BRUKINSA (zanubrutinib) in patients with relapsed/refractory (R/R) marginal zone lymphoma; and
Updated results from a Phase 2 trial showing tolerability and efficacy of zanubrutinib in patients with B-cell malignancies who were intolerant to acalabrutinib.
"BeiGene has established a solid foundation in both the research and development of innovative medicines for hematologic malignancies," said Mehrdad Mobasher, M.D., M.P.H., Chief Medical Officer, Hematology at BeiGene. "At this year’s ASH (Free ASH Whitepaper) meeting, we look forward to sharing a wealth of data from our broad, global development programs. We will showcase our deep expertise and drive to innovate — from the Phase 1 data for our novel Bcl2 inhibitor, BGB-11417 and through numerous presentations demonstrating meaningful clinical efficacy and a consistent safety profile for BRUKINSA across several B-cell malignancies."

Additional presentations highlight combinability and strength of pipeline

Preliminary safety and efficacy of zanubrutinib in combination with lenalidomide in patients with R/R diffuse large B-cell lymphoma;
Multiple posters for Phase 1 studies with BGB-11417 as monotherapy or in combination, showing promising efficacy in B-cell and myeloid malignancies, along with a manageable safety profile; and
Safety and efficacy of zanubrutinib in combination with zandelisib in patients with R/R follicular lymphoma or mantle cell lymphoma.
Investor event

BeiGene will host an ancillary event in New Orleans on December 11 at 8:00 pm CST for investors and analysts attending ASH (Free ASH Whitepaper). BeiGene senior management will review highlights of the presented data, and special guests will join them for a Q&A panel. The event will be webcast live and it can be accessed from the investors section of BeiGene’s website at View Source, View Source or View Source An archived replay will be posted for 90 days following the event.

Hematologic

Malignancy

Title

Presentation details

Oral

R/R Follicular Lymphoma

R/R Mantle Cell Lymphoma

Safety and Efficacy of the PI3Kδ Inhibitor Zandelisib in Combination with the BTK Inhibitor Zanubrutinib in Patients with Relapsed/Refractory (R/R) Follicular Lymphoma (FL) or Mantle Cell Lymphoma (MCL)

#78

Date: 12/10/2022

Time: 10:45 AM

R/R Marginal Zone Lymphoma

Long-Term Efficacy and Safety of Zanubrutinib in Patients With Relapsed/Refractory (R/R) Marginal Zone Lymphoma (MZL): Final Analysis of the MAGNOLIA (BGB-3111-214) Trial

#234

Date: 12/10/2022

Time: 3:15 PM

Chronic Lymphocytic Leukemia

Small Lymphocytic Leukemia

A Phase 1 Study With The Novel B-Cell Lymphoma 2 (Bcl-2) Inhibitor BGB-11417 As

Monotherapy or in Combination With Zanubrutinib (ZANU) in Patients (Pts) With CLL/SLL: Preliminary Data

#962

Date: 12/12/2022

Time: 4:45 PM

Poster

B-Cell Malignancies

Efficacy and Safety of Zanubrutinib in Japanese Patients With Mature B-Cell Malignancies

#1590

Date: 12/10/2022

Time: 5:30 – 7:30 PM

B-Cell Malignancies

Zanubrutinib in Acalabrutinib-Intolerant Patients (Pts) with B-Cell Malignancies

#1587

Date: 12/10/2022

Time: 5:30 – 7:30 PM

R/R Diffuse Large B-Cell Lymphoma

Preliminary Safety and Efficacy of Zanubrutinib in Combination With Lenalidomide in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma

#1627

Date: 12/10/2022

Time: 5:30 – 7:30 PM

R/R B-Cell Malignancies

Biomarker Analysis of Zanubrutinib and Tislelizumab Combination Therapy in Patients with Relapsed/Refractory B-Cell Malignancies

#1529

Date: 12/10/2022

Time: 5:30 – 7:30 PM

Acute Myeloid Leukemia

Preliminary Safety and Efficacy of BGB-11417, a Novel BCL2 Inhibitor, in Combination With Azacitidine in Patients With Acute Myeloid Leukemia (AML)

#1443

Date: 12/10/2022

Time: 5:30 – 7:30 PM

Mature B-cell Malignancies

A Phase 1 Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of BCL2 Inhibitor BGB-11417 in Adult Patients With Mature B-cell Malignancies: Preliminary Data

#2989

Date: 12/11/2022

Time: 6:00 – 8:00 PM

Multiple Myeloma

Preliminary Safety and Efficacy of a BCL-2 Inhibitor, BGB-11417, in Patients With Relapsed/Refractory Multiple Myeloma Harboring t(11,14): A Non-randomized, Open-label, Phase 1b/2 Study

#3235

Date: 12/11/2022

Time: 6:00 – 8:00 PM

Relapsed/Refractory B-Cell Malignancies

Genomic Characterization of Patients in Phase 2 Study of Zanubrutinib in BTK Inhibitor-Intolerant Patients With Relapsed/Refractory B-Cell Malignancies

#4176

Date: 12/12/2022

Time: 6:00 – 8:00 PM

Non-Hodgkin’s Lymphoma

Waldenström Macroglobulinemia

A Phase 1 Study With the Novel B-Cell Lymphoma 2 (Bcl-2) Inhibitor BGB-11417 As Monotherapy or in Combination with Zanubrutinib (ZANU) in Patients (Pts) With Non-Hodgkin’s Lymphoma (NHL) or Waldenström macroglobulinemia (WM): Preliminary Data

#4201

Date: 12/12/2022

Time: 6:00 – 8:00 PM

R/R Mantle Cell Lymphoma

Long-Term Outcomes of Second-Line vs Later-Line Zanubrutinib Treatment in Patients With Relapsed/Refractory MCL: An Updated Pooled Analysis

#2894

Date: 12/11/2022
Time: 6:00 – 8:00 PM

Online Only

RWE

Real-World Evidence (RWE) Studies Supported By Hematologic Oncology FDA Approval: What Do They Look Like

RWE

Development of Hypertension and Atrial Fibrillation Following Diagnosis of B-Cell Malignancies – A Retrospective Analysis of US MarketScan Insurance Claims Database

About BRUKINSA

BRUKINSA (zanubrutinib) is a small-molecule inhibitor of Bruton’s tyrosine kinase (BTK) discovered by BeiGene scientists that is currently being evaluated globally in a broad clinical program as a monotherapy and in combination with other therapies to treat various B-cell malignancies. BRUKINSA was specifically designed to deliver targeted and sustained inhibition of the BTK protein by optimizing bioavailability, half-life, and selectivity. With differentiated pharmacokinetics compared to other approved BTK inhibitors, BRUKINSA has been demonstrated to inhibit the proliferation of malignant B cells within a number of disease-relevant tissues.

BRUKINSA is supported by a broad clinical program which includes more than 4,500 subjects in 35 trials across 28 markets. To date, BRUKINSA has received approvals covering more than 55 countries and regions, including the United States, China, the EU, Switzerland, Great Britain, Canada, Australia, and additional international markets.

About BGB-11417

BGB-11417 is a highly potent and selective Bcl-2 inhibitor designed to produce deeper and more sustained target inhibition.

Compared with venetoclax, BGB-11417 exhibited greater potency (>10-fold) and higher target selectivity and showed signs of overcoming treatment resistance in pre-clinical studies and tumor models i

BRUKINSA IMPORTANT SAFETY INFORMATION AND U.S. INDICATIONS

Warnings and Precautions

Hemorrhage

Fatal and serious hemorrhagic events have occurred in patients with hematological malignancies treated with BRUKINSA monotherapy. Grade 3 or higher hemorrhage events including intracranial and gastrointestinal hemorrhage, hematuria and hemothorax have been reported in 3.4% of patients treated with BRUKINSA monotherapy. Hemorrhage events of any grade occurred in 35% of patients treated with BRUKINSA monotherapy.

Bleeding events have occurred in patients with and without concomitant antiplatelet or anticoagulation therapy. Co-administration of BRUKINSA with antiplatelet or anticoagulant medications may further increase the risk of hemorrhage.

Monitor for signs and symptoms of bleeding. Discontinue BRUKINSA if intracranial hemorrhage of any grade occurs. Consider the benefit-risk of withholding BRUKINSA for 3-7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding.

Infections

Fatal and serious infections (including bacterial, viral, or fungal) and opportunistic infections have occurred in patients with hematological malignancies treated with BRUKINSA monotherapy. Grade 3 or higher infections occurred in 27% of patients, most commonly pneumonia. Infections due to hepatitis B virus (HBV) reactivation have occurred.

Consider prophylaxis for herpes simplex virus, pneumocystis jiroveci pneumonia and other infections according to standard of care in patients who are at increased risk for infections. Monitor and evaluate patients for fever or other signs and symptoms of infection and treat appropriately.

Cytopenias

Grade 3 or 4 cytopenias, including neutropenia (26%), thrombocytopenia (11%) and anemia (8%) based on laboratory measurements, were reported in patients treated with BRUKINSA monotherapy. Grade 4 neutropenia occurred in 13% of patients, and Grade 4 thrombocytopenia occurred in 3.6% of patients.

Monitor complete blood counts regularly during treatment and interrupt treatment, reduce the dose, or discontinue treatment as warranted. Treat using growth factor or transfusions, as needed.

Second Primary Malignancies

Second primary malignancies, including non-skin carcinoma, have occurred in 14% of patients treated with BRUKINSA monotherapy. The most frequent second primary malignancy was non-melanoma skin cancer, reported in 8% of patients. Other second primary malignancies included malignant solid tumors (4.0%), melanoma (1.7%) and hematologic malignancies (1.2%). Advise patients to use sun protection and monitor patients for the development of second primary malignancies.

Cardiac Arrhythmias

Atrial fibrillation and atrial flutter were reported in 3.2% of patients treated with BRUKINSA monotherapy. Patients with cardiac risk factors, hypertension, and acute infections may be at increased risk. Grade 3 or higher events were reported in 1.1% of patients treated with BRUKINSA monotherapy. Monitor signs and symptoms for atrial fibrillation and atrial flutter and manage as appropriate.

Embryo-Fetal Toxicity

Based on findings in animals, BRUKINSA can cause fetal harm when administered to a pregnant woman. Administration of zanubrutinib to pregnant rats during the period of organogenesis caused embryo-fetal toxicity including malformations at exposures that were 5 times higher than those reported in patients at the recommended dose of 160 mg twice daily. Advise women to avoid becoming pregnant while taking BRUKINSA and for 1 week after the last dose. Advise men to avoid fathering a child during treatment and for 1 week after the last dose.

If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.

Adverse reactions

The most common adverse reactions, including laboratory abnormalities, in ≥ 30% of patients who received BRUKINSA (N = 847) included decreased neutrophil count (54%), upper respiratory tract infection (47%), decreased platelet count (41%), hemorrhage (35%), decreased lymphocyte count (31%), rash (31%) and musculoskeletal pain (30%).

Drug Interactions

CYP3A Inhibitors: When BRUKINSA is co-administered with a strong CYP3A inhibitor, reduce BRUKINSA dose to 80 mg once daily. For coadministration with a moderate CYP3A inhibitor, reduce BRUKINSA dose to 80 mg twice daily.

CYP3A Inducers: Avoid coadministration with moderate or strong CYP3A inducers.

Specific Populations

Hepatic Impairment: The recommended dose of BRUKINSA for patients with severe hepatic impairment is 80 mg orally twice daily.

INDICATIONS

BRUKINSA is a kinase inhibitor indicated for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.
This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
BRUKINSA is indicated for the treatment of adult patients with Waldenström’s macroglobulinemia (WM).
BRUKINSA is indicated for the treatment of adult patients with relapsed or refractory marginal zone lymphoma (MZL) who have received at least one anti-CD20-based regimen.
This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Please see full U.S. Prescribing Information at www.beigene.com/PDF/BRUKINSAUSPI.pdf and Patient Information at www.beigene.com/PDF/BRUKINSAUSPPI.pdf

BeiGene Oncology

BeiGene is committed to advancing best- and first-in-class clinical candidates internally or with like-minded partners to develop impactful and affordable medicines for patients across the globe. We have a growing R&D and medical affairs team of approximately 3,300 colleagues dedicated to advancing more than 100 clinical trials that have involved more than 16,000 subjects. Our expansive portfolio is directed predominantly by our internal colleagues supporting clinical trials in more than 45 countries and regions. Hematology-oncology, and solid tumor targeted therapies, and immuno-oncology are key focus areas for the Company, with both monotherapies and combination therapies prioritized in our research and development. BeiGene currently has three licensed medicines discovered and developed in our own labs: BTK inhibitor BRUKINSA in the U.S., China, the European Union, Switzerland, Great Britain, Canada, Australia, and additional international markets; and the non-FC-gamma receptor binding anti-PD-1 antibody tislelizumab as well as the poly adenosine diphosphate-ribose polymerase (PARP) inhibitor pamiparib in China.

BeiGene also partners with innovative companies who share our goal of developing therapies to address global health needs. We commercialize a range of oncology medicines in China licensed from Amgen, Bristol Myers Squibb, EUSA Pharma, and Bio-Thera. We also plan to address greater areas of unmet need globally through our other collaborations including Mirati Therapeutics, Seagen, and Zymeworks.

In January 2021 BeiGene and Novartis announced a collaboration granting Novartis rights to co-develop, manufacture, and commercialize BeiGene’s anti-PD-1 antibody tislelizumab in North America, Europe, and Japan. Building upon this productive collaboration, BeiGene and Novartis announced an option, collaboration, and license agreement in December 2021 for BeiGene’s TIGIT inhibitor ociperlimab that is in Phase 3 development. Novartis and BeiGene also entered into a strategic commercial agreement through which BeiGene will promote five approved Novartis oncology products across designated regions of China.

On November 3, 2022 Geron Corporation (Nasdaq: GERN), a late-stage clinical biopharmaceutical company developing a first-in-class telomerase inhibitor, imetelstat, to treat hematologic malignancies, reported financial results for the third quarter of 2022 and upcoming expected milestones (Press release, Geron, NOV 3, 2022, View Source [SID1234623011]).

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"Throughout the year, we have highlighted our vision for Geron to become a leader in the treatment of hematologic malignancies through the expected development and commercialization of imetelstat. We continue to believe that the differentiating qualities of imetelstat, including potential for disease modification and durability of effect, could transform the treatment landscape for lower risk myelodysplastic syndromes and JAK inhibitor relapsed/refractory myelofibrosis," said John A. Scarlett, M.D., Geron’s Chairman and Chief Executive Officer. "We’re looking forward to the IMerge Phase 3 top-line results expected in just two months that if positive, will advance the company from late-stage development to commercialization and provide meaningful value for stockholders and patients."

Upcoming Expected Milestones

2022

Phase 2 and non-clinical updates expected at upcoming medical meeting
Open remaining selected clinical sites in Phase 3 IMpactMF trial evaluating imetelstat vs. best available therapy in patients with JAK inhibitor relapsed/refractory myelofibrosis
Start Phase 2 IMpress investigator-led study of single-agent imetelstat in relapsed/refractory (R/R) acute myeloid leukemia (AML) and higher risk MDS
2023

Top-line results from IMerge Phase 3 in lower risk myelodysplastic syndromes (MDS) in early January
New Drug Application submission in lower risk MDS in the U.S. in the first half of the year
Marketing Authorization Application submission in lower risk MDS in the EU in the second half of the year
Preliminary data from IMproveMF Phase 1 study of imetelstat in combination with ruxolitinib in frontline myelofibrosis by year-end
2024

U.S. approval and commercial launch in lower risk MDS in the first half of the year
IMpactMF interim analysis
Current and Projected Financial Resources

As of September 30, 2022, the Company had approximately $195 million in cash and marketable securities.

Under current planning assumptions, the Company projects its existing capital resources plus projected future proceeds of up to approximately $121 million from the potential exercise of the currently outstanding warrants and up to $50 million from the current debt facility will be sufficient to fund Geron’s estimated level of operations, which includes stage-gated activities for potential U.S. commercial launch of imetelstat in lower risk MDS, until the middle of 2024.

Third Quarter 2022 Results

For the third quarter of 2022, the Company reported a net loss of $41.1 million, or $0.10 per share, compared to $26.7 million, or $0.08 per share, for the comparable 2021 period. Net loss for the first nine months of 2022 was $99.3 million, or $0.26 per share, compared to $84.1 million, or $0.26 per share, for the comparable 2021 period.

Revenues for the three and nine months ended September 30, 2022, were $297,000 and $493,000, respectively, compared to $109,000 and $353,000 for the comparable 2021 periods. Revenues in both years primarily reflect estimated royalties from sales of cell-based research products from the Company’s divested stem cell assets.

Total operating expenses for the three and nine months ended September 30, 2022, were $40.2 million and $97.1 million, respectively, compared to $25.8 million and $83.4 million for the comparable 2021 periods.

Research and development expenses for the three and nine months ended September 30, 2022, were $24.6 million and $67.3 million, respectively, compared to $18.5 million and $61.6 million for the comparable 2021 periods. The increase in research and development expenses for the three and nine months ended September 30, 2022, compared to the same periods in 2021, primarily reflects the net result of increased personnel-related expenses for additional headcount and higher consulting costs related to preparation for top-line results and regulatory submissions in lower risk MDS; partially offset by decreased manufacturing costs due to the timing of imetelstat manufacturing batches.

General and administrative expenses for the three and nine months ended September 30, 2022, were $15.6 million and $29.8 million, respectively, compared to $7.3 million and $21.8 million for the comparable 2021 periods. The increase in general and administrative expenses for the three and nine months ended September 30, 2022, compared to the same periods in 2021, primarily reflects increased costs for commercial preparatory activities; higher personnel-related expenses for additional headcount; and approximately $7.0 million for Geron’s portion of the settlement for the class action lawsuit. In September 2022, the Company entered into a Stipulation and Agreement of Settlement (Stipulation) to resolve the class action lawsuit against the Company and certain officers of the Company. Under the terms of the Stipulation, in exchange for the release and dismissal with prejudice of all claims against the defendants in the class action lawsuit, Geron agreed to pay and/or to cause the Company’s insurance carriers to pay a total of $24 million, comprised of approximately $17 million in cash and, at Geron’s election, approximately $7 million in either shares of Geron common stock and/or cash. The proposed settlement does not constitute an admission of fault or wrongdoing by Geron or its officers. The proposed settlement remains subject to final approval by the court to be conducted at a hearing scheduled at the end of the first quarter of 2023 and certain other conditions, at which time payment of the settlement amount will be due.

Interest income was $852,000 and $1.3 million for the three and nine months ended September 30, 2022, respectively, compared to $112,000 and $421,000 for the same periods in 2021. The increase in interest income for the three and nine months ended September 30, 2022, compared to the same periods in 2021, primarily reflects a larger marketable securities portfolio with the receipt of net cash proceeds from the underwritten public offering completed in April 2022 and higher yields from recent marketable securities purchases.

Interest expense was $1.8 million and $4.9 million for the three and nine months ended September 30, 2022, respectively, compared to $1.1 million and $2.6 million for the same periods in 2021. The increase in interest expense for the three and nine months ended September 30, 2022, compared to the same periods in 2021, primarily reflects rising interest rates and increased principal debt balance. Currently, the Company has $50.0 million in principal debt outstanding.

Net other expense was $138,000 and $77,000 for the three months ended September 30, 2022 and 2021, respectively. Net other income was $916,000 and $1.1 million for the nine months ended September 30, 2022 and 2021, respectively. In the second quarter of 2022, the Company recognized other income of approximately $1.3 million related to the reimbursement of certain legal expenses under its insurance policies. During the first quarter of 2021, the Company sold all of its holdings in an equity investment resulting in a net realized gain of $1.2 million, including foreign currency translation adjustments.

Projected 2022 Financial Guidance Reaffirmed

For fiscal year 2022, under generally accepted accounting principles (GAAP), the Company continues to expect total operating expenses in the range of approximately $155 million to $165 million, which includes non-cash items such as: stock-based compensation expense, amortization of debt discounts and issuance costs as well as depreciation and amortization. The Company continues to expect non-GAAP total operating expenses for fiscal year 2022, which excludes estimated non-cash items such as: stock-based compensation expense, amortization of debt discounts and issuance costs as well as depreciation and amortization, in the range of approximately $140 million to $150 million.

The fiscal year 2022 financial guidance reflects costs to support: (a) preparatory activities for top-line results from the IMerge Phase 3 clinical trial and readiness for potential regulatory filings and commercialization of imetelstat in lower risk MDS; (b) continued conduct of IMerge and IMpactMF and commencement of new clinical studies associated with the imetelstat pipeline expansion strategy; (c) finalizing validation batches of imetelstat at contract manufacturers to enable future production of imetelstat for clinical and commercial purposes; (d) projected increases in headcount and (e) interest payments on outstanding debt.

As of September 30, 2022, the Company had 98 employees. The Company plans to grow to a total of approximately 100 to 110 employees by year-end 2022.

Conference Call

Geron will host a conference call at 9:00 a.m. ET on Thursday, November 3, 2022 to review recent events and third quarter 2022 financial results.

A live webcast of the conference call and related presentation will be available on the Company’s website at www.geron.com/investors/events. An archive of the webcast will be available on the Company’s website for 30 days.

Participants may access the webcast by registering online using the following link: View Source

About Imetelstat

Imetelstat is a novel, first-in-class telomerase inhibitor exclusively owned by Geron and being developed in hematologic malignancies. Data from Phase 2 clinical trials provide strong evidence that imetelstat targets telomerase to inhibit the uncontrolled proliferation of malignant stem and progenitor cells in myeloid hematologic malignancies resulting in malignant cell apoptosis and potential disease-modifying activity. Imetelstat has been granted Fast Track designation by the United States Food and Drug Administration for both the treatment of patients with non-del(5q) lower risk MDS who are refractory or resistant to an erythropoiesis stimulating agent and for patients with Intermediate-2 or High-risk MF whose disease has relapsed after or is refractory to janus associated kinase (JAK) inhibitor treatment.

About IMerge Phase 3

IMerge Phase 3 is a double-blind, randomized, placebo-controlled Phase 3 clinical trial with registrational intent. The trial is designed to enroll approximately 170 transfusion dependent patients with Low or Intermediate-1 risk myelodysplastic syndromes (MDS), also referred to as lower risk MDS, who have relapsed after or are refractory to prior treatment with an erythropoiesis stimulating agent (ESA). The primary endpoint is the rate of red blood cell (RBC) transfusion independence (TI) for any consecutive period of eight weeks or longer, or 8-week RBC-TI rate. Key secondary endpoints include the rate of RBC-TI lasting at least 24 weeks, or 24-week RBC-TI rate, duration of TI and the rate of hematologic improvement-erythroid (HI-E), defined as a reduction of at least four units of RBC transfusions over eight weeks compared with the prior RBC transfusion burden.

IMerge Phase 3 is fully enrolled and patient enrollment has been closed. For additional information about IMerge Phase 3, visit ClinicalTrials.gov/NCT02598661.

About IMpactMF Phase 3

IMpactMF is an open label, randomized, controlled Phase 3 clinical trial with registrational intent. The trial is designed to enroll approximately 320 patients with Intermediate-2 or High-risk myelofibrosis (MF) who are relapsed after or refractory to prior treatment with a JAK inhibitor, also referred to as relapsed/refractory MF. Patients will be randomized to receive either imetelstat or best available therapy. The primary endpoint is overall survival (OS). Key secondary endpoints include symptom response, spleen response, progression free survival, complete remission, partial remission, clinical improvement, duration of response, safety, pharmacokinetics, and patient reported outcomes.

IMpactMF is currently enrolling patients. For further information about IMpactMF, including enrollment criteria, locations and current status, visit ClinicalTrials.gov/NCT04576156.

On November 3, 2022 Selecta Biosciences, Inc. (NASDAQ: SELB), a biotechnology company pioneering precision immune tolerance with its clinically validated ImmTOR platform to develop tolerogenic therapies for autoimmune diseases, unlock the potential of gene therapies and amplify the efficacy of biologic therapies, reported financial results for the third quarter ended September 30, 2022 and provided a business update (Press release, Selecta Biosciences, NOV 3, 2022, View Source [SID1234623010]).

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"We are pleased with the steady progress seen across our clinical and pre-clinical pipelines. With expected financial runway into mid-2024 we believe we are well-positioned to execute on our key priorities and achieve multiple near-term value driving inflection points," said Carsten Brunn, Ph.D., president and chief executive officer of Selecta. "Clinically, we remain on track to initiate the Phase 1 trial of SEL-302, our wholly owned gene therapy in combination with ImmTOR for the treatment of MMA in Q4 2022, and expect to report joint topline data from the Phase 3 DISSOLVE clinical program investigating SEL-212 in chronic refractory gout, in Q1 2023. Preclinically, with our external partners we continue to drive toward candidate selection for an IgA protease to treat IgA nephropathy, as well as progress IND-enabling studies and manufacturing scale-up for Xork, our proprietary IgG protease developed as a pre-treatment to enable AAV gene therapies. Finally, building on the recently presented data at ESGCT, we continue our work in identifying a proprietary IL-2 to combine with ImmTOR, which we anticipate announcing by year-end. We believe ImmTOR- IL, based on the synergistic effects we have observed preclinically, has the potential to be a generational leap forward for our precision immune tolerance platform."

Recent Program Highlights and Anticipated Upcoming Milestones:

Tolerogenic Therapies for Autoimmune Disease:

ImmTOR-IL: Preclinically, Selecta has observed synergistic activity when ImmTOR is combined with engineered IL-2 molecules that are selective for Tregs (ImmTOR-IL). Furthermore, when ImmTOR-IL was co-administered with an antigen of interest, the resulting data suggested that ImmTOR-IL may have profound synergistic effects in expanding antigen-specific Tregs when compared to ImmTOR alone, positioning ImmTOR-IL as a potential first-in-class antigen-specific therapy for the treatment of autoimmune disease.
Selecta continues to work with its partners to develop a next generation IL-2 molecule to combine with ImmTOR and still anticipates selecting an IL-2 candidate by year-end 2022.
Selecta continues internal work on identifying additional target indications in autoimmune disease. Selecta plans to adopt a staged development approach, starting first with diseases driven by a single pathogenic antigen, such as Primary Biliary Cholangitis (PBC), then accelerating development across related indications.
Primary biliary cholangitis (PBC): Selecta intends to co-administer ImmTOR-IL with PDC-E2, the autoantigen implicated in PBC and continues IND-enabling work for this combination.
Gene Therapies:

SEL-302 for MMA: Selecta remains on track to initiate a Phase 1/2 clinical trial of SEL-302, an AAV gene therapy combined with ImmTOR for the treatment of MMA, in the fourth quarter of 2022.
SEL-018 IgG Protease (Xork): In collaboration with Genovis, Selecta continues to advance Xork, a next-generation IgG protease, to help address disease in patients who are ineligible for gene therapies due to pre-existing anti-AAV antibodies. Selecta believes the novel combination of Xork and ImmTOR has the potential to address two of the key hurdles in gene therapy today: pre-existing immunity to AAVs and the inability to re-dose AAV gene therapies due to the immune response to AAV capsids.
IND-enabling studies and manufacturing scale-up activities are ongoing.
ImmTOR-IL: In October 2022, we presented preclinical data at the 29th Annual European Society of Gene and Cell Therapy (ESGCT) Conference further supporting the potential therapeutic utility of ImmTOR in enabling safe repeated vector dosing and mitigating unwanted immune responses. Additionally, we presented data in which we observed the potential of ImmTOR-IL in driving antigen-specific Treg expansion while synergistically inhibiting formation of anti-AAV antibodies at high vector doses.
Biologic Therapies:

SEL-212 for chronic refractory gout: Selecta continues to advance DISSOLVE, the Phase 3 development program of SEL-212, which has been licensed to Sobi.
In Q3 2022, Selecta received a $10 million milestone payment from Sobi following the completion of enrollment of DISSOLVE II in June 2022.
DISSOLVE I & II trials are on track for completion in Q1 2023 with joint topline readout expected in Q1 2023.
ImmTOR with IgA protease for IgA nephropathy: Selecta continues to work with its partners to identify and develop a next generation IgA protease to combine with ImmTOR, and consistent with prior guidance anticipates selecting an enzyme candidate by year-end 2022.
Further Corporate and Partnership Updates:

In Q3 2022, and as previously disclosed, Selecta received a $2 million payment from Sarepta relating to the extension of its Research License and Option Agreement for ImmTOR in Duchenne Muscular Dystrophy (DMD) and certain Limb-Girdle Muscular Dystrophies (LGMD) for an additional nine months to Q1 2023, and an additional $4 million payment from Sarepta for achievement of certain preclinical milestones.
Third Quarter 2022 Financial Results

Cash Position: Selecta had $148.0 million in cash, cash equivalents, marketable securities, and restricted cash as of September 30, 2022, as compared to cash, cash equivalents, marketable securities, and restricted cash of $129.4 million as of December 31, 2021. Net cash used in operating activities was $19.8 million for the nine months ended September 30, 2022, as compared to $28.9 million of cash used in operating activities for the same period in 2021. Selecta believes its available cash, cash equivalents, restricted cash, and marketable securities will be sufficient to meet its operating requirements into mid-2024.

Collaboration and License Revenue: Collaboration and license revenue for the third quarter of 2022 was $20.7 million, as compared to $24.4 million for the same period in 2021. Revenue was primarily driven by the shipment of clinical supply and the reimbursement of costs incurred for the Phase 3 DISSOLVE clinical program under the license agreement with Sobi.

Research and Development Expenses: Research and development expenses for the third quarter of 2022 were $16.5 million, as compared to $21.0 million for the same period in 2021. The decrease in cost was primarily the result of a decrease in expenses incurred for the SEL-212 clinical program, preclinical programs, and the AskBio collaboration.

General and Administrative Expenses: General and administrative expenses for the third quarter of 2022 were $5.8 million, as compared to $5.4 million for the same period in 2021. The increase in costs was primarily the result of expenses incurred for stock compensation and personnel expenses.

Net loss: For the third quarter of 2022, Selecta reported net loss of $7.9 million, or basic net loss per share of $0.05, compared to net loss of $17.9 million, or basic net loss per share of $0.16, for the same period in 2021.

Conference Call and Webcast Reminder
Selecta management will host a conference call at 8:30 AM ET today to provide a business update and review the company’s third quarter 2022 financial results. Individuals may participate in the live call via telephone by dialing (844) 845-4170 (domestic) or +1 (412) 717-9621 (international) and may access a teleconference replay for one week by dialing (877) 344-7529 (domestic) or +1 (412) 317-0088 (international) and using confirmation code 10157874. Investors and the public can access the live and archived webcast of this call and a copy of the presentation via the Investors & Media section of the company’s website, www.selectabio.com.

On November 3, 2022 Protara Therapeutics, Inc. (Nasdaq: TARA), a clinical-stage company developing transformative therapies for the treatment of cancer and rare diseases, reported financial results for the third quarter ended September 30, 2022 and provided a business update (Press release, Protara Therapeutics, NOV 3, 2022, View Source [SID1234623009]).

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"We continue to make meaningful progress with dose escalation in the ongoing Phase 1a portion of our ADVANCED-1 study of TARA-002 in non-muscle invasive bladder cancer (NMIBC), and look forward to ultimately utilizing these data, as well as data from our ongoing preclinical work, to design effective later-stage clinical trials in this indication," said Jesse Shefferman, Chief Executive Officer of Protara Therapeutics. "We are pleased to share that we have received initial feedback from the U.S. Food and Drug Administration (FDA) on our proposed Phase 2 study protocol evaluating TARA-002 in Lymphatic Malformations (LMs), and now expect to initiate the study in 2023. LMs represents a highly underserved rare pediatric indication for which we believe TARA-002 could serve as a much-needed treatment option."

Recent Highlights

TARA-002 in NMIBC

Dose escalation remains ongoing in the Phase 1a portion of the Company’s ADVANCED-1 clinical trial evaluating TARA-002, an investigational cell-based immunopotentiator, for the treatment of NMIBC. The Phase 1a dose escalation portion of the trial is designed to identify a safe and tolerable dose of TARA-002 to be further evaluated in the Phase 1b expansion portion of the trial.
TARA-002 in LMs

Protara recently received initial feedback from the Vaccines and Related Products Division of the FDA on the protocol for the proposed Phase 2 study evaluating TARA-002 in LMs. The Company is in the process of finalizing the trial design and expects to commence study start-up activities in the first half of 2023.
IV Choline Chloride in Intestinal Failure Associated Liver Disease (IFALD)

The Company’s prospective study to enhance understanding of the incidence of IFALD in patients dependent on parenteral nutrition remains ongoing. Protara expects to use results from the prospective study, as well as its previously completed retrospective study, to inform next steps for the IV Choline Chloride development program.
Third Quarter 2022 Financial Results

As of September 30, 2022, cash, cash equivalents and marketable debt securities were $107.1 million. The Company now expects its current cash and cash equivalents will be sufficient to fund its planned operations into the second half of 2024.
Research and development (R&D) expenses for the third quarter of 2022 decreased to $3.5 million from $4.1 million during the third quarter of 2021. The decreased R&D expenses were primarily due to lower regulatory costs relative to regulatory expense in the comparable three months ended September 30, 2021, when the Company filed its Investigational New Drug application for TARA-002.
General and administrative expenses for the third quarter of 2022 decreased to $4.5 million from $6.7 million for the prior year period. The decrease was primarily due to a decrease of $1.2 million in stock-based compensation expense, a decrease of $0.2 million in compensation, benefits and other employee-related expenses, and a decrease of $0.6 million in market development expenses.
For the third quarter of 2022, Protara reported a net loss of $7.7 million, or $0.68 per share, compared with a net loss of $10.8 million, or $0.96 per share, for the same period in 2021. Net loss for the third quarter of 2022 included approximately $1.4 million of stock-based compensation expenses.
About TARA-002

TARA-002 is an investigational cell therapy in development for the treatment of NMIBC and LMs for which it has been granted Rare Pediatric Disease Designation by the U.S. Food and Drug Administration. TARA-002 was developed from the same master cell bank of genetically distinct group A Streptococcus pyogenes as OK-432, a broad immunopotentiator marketed as Picibanil in Japan and Taiwan by Chugai Pharmaceutical Co., Ltd. Protara has successfully demonstrated manufacturing comparability between TARA-002 and OK-432.

When TARA-002 is administered, it is hypothesized that innate and adaptive immune cells within the cyst or tumor are activated and produce a strong immune cascade. Neutrophils, monocytes and lymphocytes infiltrate the abnormal cells and various cytokines, including interleukins IL-2, IL-6, IL-8, IL-10, IL-12, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor are secreted by immune cells to induce a strong local inflammatory reaction and destroy the abnormal cells.

About Non-Muscle Invasive Bladder Cancer (NMIBC)

Bladder cancer is the 6th most common cancer in the United States, with NMIBC representing approximately 80% of bladder cancer diagnoses. Approximately 65,000 patients are diagnosed with NMIBC in the United States each year. NMIBC is cancer found in the tissue that lines the inner surface of the bladder that has not spread into the bladder muscle.

About Lymphatic Malformations (LMs)

LMs are rare, congenital malformations of lymphatic vessels resulting in the failure of these structures to connect or drain into the venous system. Most LMs are present in the head and neck region and are diagnosed in early childhood during the period of active lymphatic growth, with more than 50% detected at birth and 90% diagnosed before the age of 3 years. The most common morbidities and serious manifestations of the disease include compression of the upper aerodigestive tract, including airway obstruction requiring intubation and possible tracheostomy dependence; intralesional bleeding; impingement on critical structures, including nerves, vessels, lymphatics; recurrent infection, and cosmetic and other functional disabilities.

About IV Choline Chloride and Intestinal Failure-associated Liver Disease (IFALD)

IV Choline Chloride is an investigational, intravenous (IV) phospholipid substrate replacement therapy initially in development for patients receiving parenteral nutrition (PN) who have IFALD. Choline is a known important substrate for phospholipids that are critical for healthy liver function. Because PN patients cannot sufficiently absorb adequate levels of choline and no available PN formulations contain sufficient amounts of choline to correct this deficiency, PN patients often experience a prolonged progression to hepatic failure and death, with the only known intervention being a dual small bowel/liver transplant. If approved, IV Choline Chloride would be the first approved therapy for IFALD. It has been granted Orphan Drug Designations (ODDs) by the FDA for the treatment of IFALD and the prevention of choline deficiency in PN patients.