On November 9, 2022 Galera Therapeutics, Inc. (Nasdaq: GRTX), a clinical-stage biopharmaceutical company focused on developing and commercializing a pipeline of novel, proprietary therapeutics that have the potential to transform radiotherapy in cancer, reported financial results for the third quarter ended September 30, 2022 and provided recent corporate updates (Press release, Galera Therapeutics, NOV 9, 2022, View Source [SID1234623570]).

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"During the quarter, we added to the package of data supporting our planned avasopasem New Drug Application in radiotherapy-induced severe oral mucositis, which we are on track to submit by the end of the year," said Mel Sorensen, M.D., Galera’s President and CEO. "We presented long-term follow-up data from ROMAN at ASTRO, the major annual radiation oncology conference, affirming what we saw in GT-201, specifically that avasopasem reduced severe oral mucositis while maintaining the clinical benefit of radiation therapy. Moreover, patients were also evaluated for renal function during the one-year follow-up period, and the data showed a 50% reduction in chronic kidney disease, a known cisplatin-related superoxide toxicity."

Dr. Sorensen continued: "Our market research continues to indicate that radiation and medical oncologists treating head and neck cancer view the avasopasem profile favorably and that the majority would prescribe avasopasem if approved by the FDA. The research also indicates that physicians view SOM — the most burdensome side effect of radiation therapy for head and neck cancer — as something best characterized by several key measures. These include not only whether a patient develops SOM, but also how long they suffer from it, when it first develops and whether it worsens into the most severe grade, Grade 4 OM. The meta-analysis of the already positive results from both the ROMAN and GT-201 trials underscores that avasopasem improves SOM across these measures."

Recent Corporate Updates

Radiotherapy-Induced Toxicity Programs:

Severe Oral Mucositis (SOM)

The Company remains on track to submit a New Drug Application (NDA) for avasopasem manganese 90 mg for radiotherapy-induced SOM to the U.S. Food and Drug Administration (FDA) by the end of 2022.

Long-term follow-up data from the ROMAN trial was presented in an oral presentation at the 2022 American Society for Radiation Oncology (ASTRO) Annual Meeting. After one-year follow-up on ROMAN, patients receiving avasopasem in combination with the standard-of-care regimen demonstrated comparable tumor outcomes and overall survival to patients in the placebo arm, showing that avasopasem protected patients with head and neck cancer from SOM without affecting the treatment benefit of standard-of-care chemoradiotherapy.

In a prospectively defined component of the ROMAN long-term follow-up data, also presented at ASTRO, patients treated with avasopasem in combination with radiotherapy and cisplatin had a 10% incidence of chronic kidney disease (CKD) after one year of post treatment follow-up, half the 20% rate in the placebo arm (p=0.0043). This exploratory endpoint was based on mechanism-driven non-clinical studies and a retrospective analysis of GT-201 and suggests avasopasem may offer a further benefit for these patients.

Additionally, a meta-analysis of Galera’s two randomized placebo-controlled trials (ROMAN and GT-201; n=551) was included in the ASTRO presentation, and showed clinically meaningful reductions in the incidence, duration, onset and severity of SOM compared to placebo across both trials.

A poster presentation during ASTRO highlighted the completed Phase 2 EUSOM trial of avasopasem for radiotherapy-induced SOM in Europe.
Esophagitis

Final data from the open-label, single-arm Phase 2 AESOP trial of avasopasem for severe acute radiotherapy-induced esophagitis in patients with lung cancer receiving concurrent chemoradiotherapy were presented at ASTRO. The Company previously reported positive topline data from the trial demonstrating that avasopasem was well tolerated and the incidence of Grade 3 esophagitis was substantially reduced in comparison to expectations based on review of historical data in the literature. No patients experienced Grade 4 or 5 esophagitis at any point during the AESOP trial.
Anti-Cancer Programs:

Locally Advanced Pancreatic Cancer (LAPC)

Enrollment is ongoing in the randomized, placebo-controlled Phase 2b GRECO-2 trial of rucosopasem in combination with stereotactic body radiation therapy (SBRT) in patients with LAPC. The primary endpoint of the trial is overall survival. Completion of enrollment is expected in the second half of 2023.
Non-Small Cell Lung Cancer (NSCLC)

A poster presentation at ASTRO highlighted the ongoing randomized, placebo-controlled Phase 2 stage of the GRECO-1 trial of rucosopasem in combination with SBRT in patients with NSCLC. Completion of enrollment in the Phase 2 stage of this trial is expected in the second half of 2023.
General Corporate Updates:

The Company appointed Eugene P. Kennedy, M.D., F.A.C.S., as Chief Medical Officer. Dr. Kennedy is a renowned Johns Hopkins-trained surgical oncologist and former Chief of Pancreatic and Hepatobiliary Surgery at Thomas Jefferson University with over 15 years’ experience in clinical development and biopharma leadership. He will succeed Jon T. Holmlund, M.D., who plans to retire at the end of this year following the planned submission of the Company’s NDA for avasopasem to the FDA.
Third Quarter 2022 Financial Highlights

Research and development expenses were $8.1 million in the third quarter of 2022, compared to $14.8 million for the same period in 2021. The decrease was primarily attributable to a decrease in avasopasem development costs, partially offset by an increase in rucosopasem development costs.

General and administrative expenses were $4.9 million in the third quarter of 2022, compared to $5.5 million for the same period in 2021. The decrease was primarily attributable to the timing of spend for avasopasem commercial preparations.
Galera reported a net loss of ($16.0) million, or $(0.60) per share, for the third quarter of 2022, compared to a net loss of $(22.6) million, or $(0.86) per share, for the same period in 2021.

As of September 30, 2022, Galera had cash, cash equivalents and short-term investments of $42.8 million. Galera expects that its existing cash, cash equivalents and short-term investments will enable Galera to fund its operating expenses and capital expenditure requirements into the second half of 2023.

On November 9, 2022 Immunocore Holdings plc (Nasdaq: IMCR) ("Immunocore" or the "Company"), a commercial-stage biotechnology company pioneering the development of a novel class of T cell receptor (TCR) bispecific immunotherapies designed to treat a broad range of diseases, including cancer, autoimmune and infectious diseases, reported its financial results for the third quarter ended September 30, 2022 and provided a business update (Press release, Immunocore, NOV 9, 2022, View Source [SID1234623569]).

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"We are proud to have delivered the world’s first soluble TCR therapy to patients, and to have achieved such uptake in academic and community treatment centers," commented Bahija Jallal, Chief Executive Officer of Immunocore. "The promising clinical data from our PRAME candidate, presented at ESMO (Free ESMO Whitepaper) Congress 2022, has demonstrated the potential of our platform in multiple tumor types and confirmed that there is high and homogeneous expression of the antigen across these tumors. We are recruiting patients in the expansion arms of the Phase 1/2 trial to further assess efficacy."

"With the strong commercial performance of KIMMTRAK, our PIPE financing in the third quarter, and the refinancing of the existing debt facility on improved terms, we are well-positioned to confidently deliver the next stages of the Company’s growth, including the further development of the PRAME clinical program," commented Brian Di Donato, Chief Financial Officer & Head of Strategy of Immunocore.

Third Quarter 2022 Highlights (including post-period)

KIMMTRAK (tebentafusp-tebn)

Total net product and net pre-product revenue arising from the sale of KIMMTRAK and tebentafusp was £36.3 million (or $40.4 million) in the three months ended September 30, 2022, an increase of 20% in USD over 2Q 2022 (converted using respective end-of-period convenience rates), and £74.5 million (or $83.0 million) in the nine months ended September 30, 2022.

During the third quarter of 2022, the Company continued to add new accounts prescribing KIMMTRAK in the United States, Germany, and France. As of September 30, there were 180 new accounts prescribing KIMMTRAK in the United States, which brings the capture rate of these accounts, according to the company’s estimates, to 50% of potentially eligible patients. There were 80 new accounts prescribing KIMMTRAK in Germany and France, which brings the capture rate to approximately 70% of the eligible patient population. In September, the Company began selling KIMMTRAK as a commercial product in France, and these net sales are reflected in product revenue.

KIMMTRAK’s clinical benefit to patients continues to be recognized, with the G-BA (Gemeinsamer Bundesausschuss) granting a considerable added benefit rating to KIMMTRAK. KIMMTRAK is one of only two orphan oncology medicines for rare diseases to receive a considerable added benefit rating – the second-highest possible – in more than ten years of the German reimbursement process, Arzneimittelmarkt-Neuordnungsgesetz (AMNOG). This recommendation builds upon the positive recommendations by American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) and National Comprehensive Cancer Network (NCCN) in the second quarter of this year.

In November, the Company and Medison Pharma Ltd. ("Medison") amended and restated their exclusive distribution agreement for KIMMTRAK originally entered into in September 2021. Medison is the exclusive distribution partner for KIMMTRAK in Canada, Australia, New Zealand, Israel, Central and Eastern Europe, and following this amendment South and Central America, and the Caribbean.

KIMMTRAK (tebentafusp) developmental programs

In August, the Company announced its plans to evaluate tebentafusp in a randomized Phase 2/3 trial in previously treated advanced melanoma. The trial will enroll patients with advanced melanoma, excluding uveal melanoma, who have progressed on an anti-PD1, received prior ipilimumab and, if applicable, received a tyrosine kinase inhibitor (TKI). The Phase 2 portion of the trial will include 40 patients per arm and has a dual primary endpoint of overall survival (OS) and circulating tumor DNA (ctDNA) reduction. The Company is on track to start the trial in the fourth quarter of 2022.

In September, the Company presented four posters at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2022:

A propensity score weighted comparison of tebentafusp or pembrolizumab versus combination ipilimumab and nivolumab in untreated metastatic uveal melanoma
Safety and efficacy of infrequent tebentafusp treatment omissions in patients with metastatic uveal melanoma
Long-term survivors on tebentafusp in phase 2 trial of previously treated patients with metastatic uveal melanoma
ImmTAC redirect T cells against patient-derived tumor organoids and three-dimensional melanospheres; effects augmented by type I interferons
In November, the Company had two posters accepted for presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 37th Annual Meeting. SITC (Free SITC Whitepaper) 2022 is being held November 8-12, 2022 in Boston Massachusetts. The titles of the company’s poster presentations are as follows:

Molecular features in tumors at time of progression on tebentafusp associated with overall survival (OS)
Tebentafusp induced T and B cell epitope spread in patients with advanced melanoma
IMC-F106C Targeting PRAME

In September, the initial Phase 1 data from the dose escalation study of IMC-F106C, the first off-the-shelf PRAME x CD3 ImmTAC bispecific protein, was presented as a proffered paper (oral presentation) during an "Investigational Immunotherapy" session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress. IMC-F106C demonstrated a well-tolerated safety profile. Durable RECIST responses and reduction in circulating tumor DNA (ctDNA) were observed across multiple solid tumors. Doses of ≥ 20 mcg were clinically active and had consistent and robust interferon gamma induction, a specific marker of T cell activation.

The Company has initiated patient enrollment into four expansion arms in cutaneous melanoma, ovarian, non-small cell lung cancer (NSCLC), and endometrial cancers. The Company will also study IMC-F106C in combination with standards-of-care, including with tebentafusp.

IMC-C103C Targeting MAGE-A4

Data from the Phase 1 ovarian expansion arm of the dose escalation study with IMC-C103C, the MAGE-A4 x CD3 ImmTAC bispecific protein, was accepted for a poster presentation at the ESMO (Free ESMO Whitepaper) Immuno-Oncology Congress 2022, in December. In this expansion arm, the Company enrolled all comers and evaluated MAGE expression retrospectively.

In the initial dose escalation data reported at ESMO (Free ESMO Whitepaper) I-O in December 2021, there were 15 response evaluable ovarian carcinoma patients in the active dose range (≥90 mcg). Only half were positive for MAGE-A4, with a median H score of 35 out of 300, and one patient had a confirmed partial response.

ImmTAV clinical programs

In July, the Company dosed the first patient in the first-in-human clinical trial of IMC-M113V, a new class of bispecific protein immunotherapy that is being developed for the treatment of patients with human immunodeficiency virus (HIV) infection. IMC-M113V is an immunotherapeutic approach designed to specifically eliminate CD4+ cells that are persistently infected with HIV (‘reservoirs’). IMC-M113V targets a peptide derived from the Gag protein that is presented by HLA*A02 on the surface of HIV infected cells. Reduction of the number of these cells is one way to potentially achieve a state of viral suppression in the absence of anti-retroviral medications, or a ‘functional cure’.

Corporate and financial updates

For the third quarter ended September 30, 2022, Immunocore reported net KIMMTRAK / tebentafusp revenues of £36.3 million (or $40.4 million). U.S. net product revenue from the sale of KIMMTRAK in the second quarter was £22.5 million (or $25.1 million), and European revenue (primarily in German and France) from the sale of KIMMTRAK and early access tebentafusp was £13.0 million (or $14.5 million).

Third quarter net KIMMTRAK / tebentafusp revenues of £36.3 million (or $40.4 million) increased by 31% (or 20%) compared to our previously reported second quarter KIMMTRAK / tebentafusp revenues of £27.7 million (or $33.7 million).1

In July, the Company announced a private investment in public equity ("PIPE") financing with four existing investors for net proceeds of $139.6 million. This financing, along with anticipated revenue from KIMMTRAK and cash and cash equivalents on hand, are expected to fund the Company through 2025.

The Company has entered into a loan agreement with investment funds managed by Pharmakon Advisors, LP, providing the Company with up to $100 million committed. The initial $50 million drawn from the credit facility will be used to refinance the Company’s existing debt with Oxford Finance, LLC on improved terms and the remaining $50 million, if and when drawn, is intended to be used to support the continued development and commercialization of the Company’s pipeline and for other general purposes.

Anticipated Upcoming Milestones 2022

KIMMTRAK
Q4 2022 – start the Phase 2/3 clinical trial in previously treated advanced melanoma

ImmTAC pipeline
Q4 2022 – report initial data from IMC-C103C (MAGE-A4) Phase 1 ovarian expansion arm

Financial Results

Basic and diluted earnings per share for the three months ended September 30, 2022, was £0.13 (or $0.14) and £0.12 (or $0.13), respectively, compared to a basic and diluted loss per share of (£0.69) for the three months ended September 30, 2021. Basic and diluted loss per share for the nine months ended September 30, 2022, was (£0.36) (or ($0.40)), compared to (£2.19) for the nine months ended September 30, 2021.

Total operating loss for the nine months ended September 30, 2022, was £17.3 million (or $19.2 million), compared to £97.3 million for the nine months ended September 30, 2021. For the three months ended September 30, 2022, we generated an operating profit of £6.2 million (or $6.9 million) compared to an operating loss of £31.0 million for the three months ended September 30, 2021. The operating profit of £6.2 million (or $6.9 million), for the three months ended September 30, 2022, reflects foreign exchange gains of £15.2 million (or $16.9 million) due to the significant changes arising in the exchange rates between pounds sterling and U.S. dollars during this period.

Total net product and net pre-product revenue arising from the sale of KIMMTRAK and tebentafusp was £36.3 million (or $40.4 million) in the three months ended September 30, 2022, and £74.5 million (or $83.0 million) in the nine months ended September 30, 2022. In the three and nine months ended September 30, 2021, we recorded pre-product revenue of £0.5 million.

For the three and nine months ended September 30, 2022, our research and development expenses were £23.3 million (or $25.9 million) and £62.0 million (or $69.1 million), respectively, as compared to £16.8 million and £53.2 million for the three and nine months ended September 30, 2021, respectively. For the three and nine months ended September 30, 2022, our selling and administrative expenses were £11.7 million (or $13.0 million) and £50.6 million (or $56.3 million) compared to £20.0 million and £64.0 million for the three and nine months ended September 30, 2021, respectively.

Cash and cash equivalents were £347.2 million or $386.6 million as of September 30, 2022 compared to £237.9 million as of December 31, 2021.

##

About ImmTAV molecules and infectious diseases
ImmTAV (Immune mobilising monoclonal TCRs Against Virus) molecules are novel bispecific molecules that, like ImmTAC (Immune mobilising monoclonal TCRs Against Cancer) molecules, are designed to enable the immune system to recognize and eliminate virally infected cells.

Immunocore is advancing clinical candidates to cure patients with HIV and hepatitis B virus (HBV). The Company aims to achieve sustained control of HIV after patients stop anti-retroviral therapy (ART), without the risk of virological relapse or onward transmission. This is known as ‘functional cure’. For the treatment of HBV, the Company aims to achieve sustained loss of circulating viral antigens and markers of viral replication after stopping medication for people living with chronic HBV.

About ImmTAC molecules for cancer
Immunocore’s proprietary T cell receptor (TCR) technology generates a novel class of bispecific biologics called ImmTAC (Immune mobilizing monoclonal TCRs Against Cancer) molecules that are designed to redirect the immune system to recognize and kill cancerous cells. ImmTAC molecules are soluble TCRs engineered to recognize intracellular cancer antigens with ultra-high affinity and selectively kill these cancer cells via an anti-CD3 immune-activating effector function. Based on the demonstrated mechanism of T cell infiltration into human tumors, the ImmTAC mechanism of action holds the potential to treat hematologic and solid tumors, regardless of mutational burden or immune infiltration, including immune "cold" low mutation rate tumors.

About TEBE-AM Phase 2/3 Trial
IMCgp100-203 (also known as TEBE-AM) is a randomized Phase 2/3 trial in previously treated advanced melanoma that will evaluate the effect of KIMMTRAK (tebentafsup) on overall survival (OS). The trial will enroll patients with advanced melanoma, excluding uveal melanoma, that have progressed on an anti-PD1, received prior ipilimumab and, if applicable, received a tyrosine kinase inhibitor (TKI). The Phase 2/3 trial will randomize to one of three arms including KIMMTRAK, as monotherapy or in combination with an anti-PD1, and a control arm. Patients randomized to the control arm will immediately enter overall survival (OS) follow-up where they may be treated per the investigator decision including other clinical trials. This design effectively randomizes patients to "real world" treatment since clinical trials are the preferred option. The Phase 2 portion of the trial will include 40 patients per arm and has a dual primary endpoint of OS and circulating tumor DNA (ctDNA) reduction. The Phase 3 portion currently plans to enroll 170 patients per arm and has a primary endpoint of OS. However, the design of the Phase 3 portion including eligibility, whether to discontinue an arm and powering may be adapted based on results from the Phase 2 portion.

About the IMC-F106C-101 Phase 1/2 Trial
IMC-F106C-101 is a first-in-human, Phase 1/2 dose escalation trial in patients with multiple solid tumor cancers including non-small cell lung cancer (NSCLC), small-cell lung cancer (SCLC), endometrial, ovarian, cutaneous melanoma, and breast cancers. The Phase 1 dose escalation trial was designed to determine the maximum tolerated dose (MTD), as well as to evaluate the safety, preliminary anti-tumor activity and pharmacokinetics of IMC-F106C, a bispecific protein built on Immunocore’s ImmTAC technology, and the Company’s first molecule to target the PRAME antigen. The Company has initiated patient enrollment into four expansion arms in cutaneous melanoma, ovarian, NSCLC, and endometrial cancers. The IMC-F106C-101 trial is adaptive and includes the option for Phase 2 expansion, allowing for approximately 100 patients treated per tumor type in the Phase 1 and 2 expansion arms. Dose escalation continues in additional solid tumors as well as plans for combination arms with standards-of-care.

About Uveal Melanoma
Uveal melanoma is a rare and aggressive form of melanoma, which affects the eye. Although it is the most common primary intraocular malignancy in adults, the diagnosis is rare, and up to 50% of people with uveal melanoma will eventually develop metastatic disease. Unresectable or metastatic uveal melanoma typically has a poor prognosis and had no approved treatment until KIMMTRAK.

About KIMMTRAK
KIMMTRAK is a novel bispecific protein comprised of a soluble T cell receptor fused to an anti-CD3 immune-effector function. KIMMTRAK specifically targets gp100, a lineage antigen expressed in melanocytes and melanoma. This is the first molecule developed using Immunocore’s ImmTAC technology platform designed to redirect and activate T cells to recognise and kill tumour cells. KIMMTRAK has been approved for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma in the United States, European Union, Canada, Australia, and the United Kingdom.

About Phase 3 IMCgp100-202 Trial
IMCgp100-202 (NCT03070392) is a randomized pivotal trial that evaluated overall survival (OS) of KIMMTRAK compared to investigator’s choice (either pembrolizumab, ipilimumab, or dacarbazine) in HLA-A*02:01-positive adult patients with previously untreated mUM. KIMMTRAK demonstrated an unprecedented OS benefit with a Hazard Ratio (HR) in the intent-to-treat population favoring KIMMTRAK, HR=0.51 (95% CI: 0.37, 0.71); p< 0.0001, over investigator’s choice (82% pembrolizumab; 13% ipilimumab; 6% dacarbazine).

IMPORTANT SAFETY INFORMATION

Cytokine Release Syndrome (CRS), which may be serious or life-threatening, occurred in patients receiving KIMMTRAK. Monitor for at least 16 hours following first three infusions and then as clinically indicated. Manifestations of CRS may include fever, hypotension, hypoxia, chills, nausea, vomiting, rash, elevated transaminases, fatigue, and headache. CRS occurred in 89% of patients who received KIMMTRAK with 0.8% being grade 3 or 4. Ensure immediate access to medications and resuscitative equipment to manage CRS. Ensure patients are euvolemic prior to initiating the infusions. Closely monitor patients for signs or symptoms of CRS following infusions of KIMMTRAK. Monitor fluid status, vital signs, and oxygenation level and provide appropriate therapy. Withhold or discontinue KIMMTRAK depending on persistence and severity of CRS.

Skin Reactions

Skin reactions, including rash, pruritus, and cutaneous edema occurred in 91% of patients treated with KIMMTRAK. Monitor patients for skin reactions. If skin reactions occur, treat with antihistamine and topical or systemic steroids based on persistence and severity of symptoms. Withhold or permanently discontinue KIMMTRAK depending on the severity of skin reactions.

Elevated Liver Enzymes

Elevations in liver enzymes occurred in 65% of patients treated with KIMMTRAK. Monitor alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total blood bilirubin prior to the start of and during treatment with KIMMTRAK. Withhold KIMMTRAK according to severity.

Embryo-Fetal Toxicity

KIMMTRAK may cause fetal harm. Advise pregnant patients of potential risk to the fetus and patients of reproductive potential to use effective contraception during treatment with KIMMTRAK and 1 week after the last dose.

The most common adverse reactions (≥30%) in patients who received KIMMTRAK were cytokine release syndrome, rash, pyrexia, pruritus, fatigue, nausea, chills, abdominal pain, edema, hypotension, dry skin, headache, and vomiting. The most common (≥50%) laboratory abnormalities were decreased lymphocyte count, increased creatinine, increased glucose, increased AST, increased ALT, decreased hemoglobin, and decreased phosphate.

For more information, please see full Summary of Product Characteristics (SmPC) or full U.S. Prescribing Information (including BOXED WARNING for CRS).

About KIMMTRAKConnect
Immunocore is committed to helping patients who need KIMMTRAK obtain access via our KIMMTRAKConnect program. The program provides services with dedicated nurse case managers who provide personalized support, including educational resources, financial assistance, and site of care coordination. To learn more, visit KIMMTRAKConnect.com or call 844-775-2273.

On November 9, 2022 Vividion Therapeutics, Inc., a biopharmaceutical company utilizing novel discovery technologies to unlock high value, traditionally undruggable targets with precision therapeutics for devastating cancers and immune disorders, and a wholly owned and independently operated subsidiary of Bayer AG, reported that Jenna Goldberg, M.D., has joined the company as Chief Medical Officer (Press release, Bayer, NOV 9, 2022, View Source [SID1234623568]). Dr. Goldberg brings industry leadership experience to Vividion, having held multiple senior medical roles during her career at Janssen Research and Development, a division of Johnson & Johnson.

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"Jenna has a broad and successful track record in drug development, having advanced several novel therapies through approval with focus and precision, thereby enabling patients in need to benefit from cancer breakthroughs. Jenna brings proven leadership skills, clinical development expertise and tremendous energy to our growing team," said Jeffrey Hatfield, chief executive officer of Vividion. "Her addition comes at an exciting inflection point for our growth, as we clearly see the potential to advance multiple programs into the clinic starting next year."

"I am very excited to join Vividion to continue to advance innovation in an entrepreneurial environment focused on patient benefits and outcomes," said Dr. Goldberg. "I am impressed by the pipeline’s breadth of novel, first-in-class programs in oncology and immunology. These programs are nearly all targeting proteins the industry has previously viewed as undruggable, and indicate the potential to deliver enormous value to patients if successful. I am also intrigued by the arm’s length business model established with Bayer that allows us to operate largely autonomously and independently but with the technical expertise and financial stability of a major pharmaceutical company."

Dr. Goldberg has served most recently as Vice President, Early Clinical Development, at Janssen supervising the clinical programs for multiple myeloma, cellular therapy, prostate cancer, as well as clinical pharmacology. Additionally, she served as the Co-Chair of Janssen Oncology Protocol Review Committee, since January 2021. Notably, Dr. Goldberg supervised protocol developments, successful IND submissions of numerous compounds, and all early development clinical efforts for teclistamab, talquetamab, and ciltacabtagene autoleucel, that were either granted breakthrough therapy designation or are currently approved medicines. Dr Goldberg also held other early as well as late development medical roles at Janssen over the past eight years. Prior to joining Janssen, she served as Assistant Attending Physician at Memorial Hospital/Assistant Member of Memorial Sloan-Kettering Cancer Center. Dr. Goldberg holds an M.D. from Johns Hopkins University School of Medicine and an undergraduate from Massachusetts Institute of Technology, with a Bachelor of Science in Biology. Dr. Goldberg did her postdoctoral training as a Fellow at Memorial Sloan Kettering, Cancer Center in Hematology and Oncology as well as a Fellow in Medicine, at Weill Medical College of Cornell University.

On November 9, 2022 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global biotechnology company developing and commercializing innovative and affordable oncology medicines to improve treatment outcomes and access for far more patients worldwide, reported financial results for the third quarter of 2022, recent business highlights, and anticipated upcoming milestones (Press release, BeiGene, NOV 9, 2022, View Source [SID1234623567]).

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"BeiGene generated strong product revenue in the third quarter, led by growth of our internally developed cornerstone assets, BRUKINSA and tislelizumab, and BRUKINSA has now been approved in more than 55 markets around the world," said John V. Oyler, Co-Founder, Chairman and Chief Executive Officer of BeiGene. "We are delighted with the recently reported positive topline results from the final progression-free survival analysis of BRUKINSA compared to IMBRUVICA, which supports our confidence in BRUKINSA as a potential new treatment that can provide hope for patients and families with CLL. We look forward to sharing the full data with the medical and patient communities, to important milestones in the coming months and to a strong finish for 2022."

"Our third quarter results underscore our commercial capabilities and the commitment of our more than 9,000 colleagues across 29 countries and regions to operating with excellence," said Julia Wang, Chief Financial Officer, BeiGene. "Following the close of the third quarter, our total product revenue this year has now exceeded $1 billion, an exciting milestone for the company. BeiGene is well positioned to leverage its financial strength and multiple upcoming catalysts for long-term growth."

Third Quarter 2022 Financial Results

Cash, Cash Equivalents, Restricted Cash, and Short-Term Investments were $5.1 billion as of September 30, 2022, and $6.6 billion as of December 31, 2021.

In the three months ended September 30, 2022, cash used in operating activities was $561.9 million, primarily due to our net loss of $557.6 million and an increase in our net operating assets and liabilities of $88.0 million, offset by non-cash charges of $83.7 million. Net loss for the three months ended September 30, 2022, includes $125.6 million of other losses due primarily to the strengthening of the U.S. dollar and the related revaluation of foreign currencies held by U.S. functional currency subsidiaries. Capital expenditures were $108.7 million and cash provided by financing activities was $120.2 million. In addition, the impact of foreign currency deposits being translated into the U.S. dollar negatively impacted ending cash by $62.7 million in the three months ended September 30, 2022.
Revenue for the three months ended September 30, 2022, was $387.6 million, compared to $206.4 million in the same period of 2021.

Product revenue totaled $349.5 million for the three months ended September 30, 2022, compared to $192.5 million in the same period of 2021, including:
Global sales of BRUKINSA of $155.5 million for the third quarter of 2022, compared to $65.8 million in the prior year period;
Sales of tislelizumab in China of $128.2 million for the third quarter of 2022, compared to $77.0 million in the prior year period;
Sales of Amgen in-licensed products in China of $27.5 million for the third quarter of 2022, compared to $20.8 million in the prior-year period. Prior-year period sales do not include sales of KYPROLIS, which was launched in China in January 2022; and
Sales of BMS in-licensed products in China of $22.4 million for the third quarter of 2022, compared to $26.0 million in the prior year period.
Collaboration revenue for the three months ended September 30, 2022, was $38.1 million, resulting from partial recognition of the upfront payments from Novartis of $650.0 million related to the tislelizumab agreement and $300.0 million related to the ociperlimab option agreement, which were entered into in the first quarter and fourth quarter of 2021, respectively. Collaboration revenue for the three months ended September 30, 2021, was $14.0 million, resulting from the partial recognition of revenue related to the tislelizumab agreement.
Expenses for the three months ended September 30, 2022, were $826.0 million, compared to $668.8 million in the same period of 2021.

Cost of Sales for the three months ended September 30, 2022, were $76.5 million, compared to $47.4 million in the same period of 2021. Cost of sales increased primarily due to increased product sales of BRUKINSA and tislelizumab, as well as BLINCYTO, which commenced in August 2021, and KYPROLIS and POBEVCY, which commenced in January 2022.
R&D Expenses for the three months ended September 30, 2022, were $426.4 million, compared to $351.9 million in the same period of 2021. The increase in R&D expenses was primarily attributable to increases in headcount and costs related to investment in our discovery and development activities, including our continued efforts to internalize research and clinical development activities, as well as increased upfront fees for in-process R&D. Upfront fees related to in-process R&D for in-licensed assets totaled $20.0 million and nil in the third quarters of 2022 and 2021, respectively. Employee share-based compensation expense also contributed to the overall increase in R&D expenses and was $36.4 million for the three months ended September 30, 2022, compared to $31.7 million for the same period of 2021.
SG&A Expenses for the three months ended September 30, 2022, were $322.9 million, compared to $269.2 million in the same period of 2021. The increase in SG&A expenses was primarily attributable to increased headcount, largely related to the expansion of our commercial teams, higher professional service fees and higher external commercial expenses, including selling and marketing, market access studies and promotional activities. The overall increase in SG&A expenses was also attributable to higher SG&A-related employee share-based compensation expense, which was $41.8 million and $35.4 million for the third quarters of 2022 and 2021, respectively.
Operating Loss for the three months ended September 30, 2022, decreased by $24.0 million, or 5.2%, to $438.4 million, compared to $462.3 million in the same period of 2021. The decrease in operating loss for the quarter was driven by increased gross profit on product sales, which exceeded the growth in operating expenses.
Net Loss for the quarter ended September 30, 2022, was $557.6 million, or $0.41 per share, and $5.39 per American Depositary Share (ADS), compared to $438.1 million, or $0.36 per share, and $4.72 per ADS in the same period of 2021. Net loss for the quarter was negatively impacted by other non-operating expenses of $125.6 million, primarily related to foreign exchange losses resulting from the strengthening of the U.S. dollar and the revaluation impact of foreign currencies held in U.S. functional currency subsidiaries.
Recent Business Highlights

Commercial Operations

Product sales increased 82% in the third quarter of 2022 compared to the prior-year period, primarily due to increased sales of our internally developed products, BRUKINSA and tislelizumab, as well as increased sales of in-licensed products from Amgen and Bio-Thera;
Global sales of BRUKINSA totaled $155.5 million in the third quarter, representing a 136% increase compared to the prior-year period. U.S. sales of BRUKINSA totaled $108.1 million in the third quarter, representing growth of 221% compared to the prior year period, as the U.S. prescribing base continued to grow and as clinician use increased within approved indications — mantle cell lymphoma (MCL), Waldenström’s macroglobulinemia (WM) and marginal zone lymphoma (MZL). BRUKINSA sales in China totaled $39.5 million in the third quarter, representing growth of 23% compared to the prior-year period, driven by a continued increase in all approved indications, for a leading position in the China BTK market;
Sales of tislelizumab in China totaled $128.2 million in the third quarter, representing a 67% increase compared to the prior year period. Approval of additional indications this year resulted in higher market penetration and market share in the third quarter for tislelizumab, and we saw higher new patient demand from broader reimbursement in the National Reimbursement Drug List; and
The National Institute for Health and Care Excellence (NICE) issued a final appraisal document recommending BRUKINSA for the treatment of WM in adults who have had at least one treatment, only if bendamustine plus rituximab is also suitable, marking the first and only treatment for WM to be recommended by NICE for routine use in England and Wales.
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 58 markets including the U.S., China, European Union (EU), Great Britain, Canada, Australia, South Korea and Switzerland in selected indications and under development for additional approvals globally. The global BRUKINSA development program includes more than 4,700 subjects enrolled to-date in more than 25 countries and regions.

Announced that BRUKINSA achieved superior Progression-Free Survival (PFS) versus ibrutinib in a final analysis of the Phase 3 ALPINE trial, as assessed by an independent review committee (IRC) and investigator;
Received European Commission approval for BRUKINSA for the treatment of MZL, making BRUKINSA the first and only BTK inhibitor for MZL approved in the European Union;
Received positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommending approval of BRUKINSA for the treatment of adults with chronic lymphocytic leukemia (CLL); and
Expanded BRUKINSA’s registration program globally in new geographies and indications, including launches in 10 additional markets year-to-date.
Tislelizumab, a humanized IgG4 anti-PD-1 monoclonal antibody specifically designed to minimize binding to FcγR on macrophages; approved in China in nine indications and under development for additional approvals globally. The global tislelizumab clinical development program includes more than 11,500 subjects enrolled to-date in 30 countries and regions. Highlights include:

Announced acceptance by the Center for Drug Evaluation (CDE) of the NMPA for a supplemental biologics application (sBLA) for tislelizumab in combination with chemotherapy as a first-line (1L) treatment in patients with unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC);
A new drug application of tislelizumab in 1L and second-line (2L) non-small cell lung cancer (NSCLC) and 2L esophageal cancer is under review by MedSafe in New Zealand;
A new drug application of tislelizumab in 2L esophageal cancer is under review by the South Korea Ministry of Food and Safety (MFDS);
Announced that the global Phase 3 RATIONALE 301 trial with tislelizumab met its primary endpoint of non-inferior Overall Survival (OS) versus sorafenib as a 1L treatment in adult patients with unresectable hepatocellular carcinoma (HCC). These data were accepted as a late-breaking abstract and presented in an oral session at the European Society for Medical Oncology Congress 2022 (ESMO 2022);
Shared a poster demonstrating a consistent response for tislelizumab in RATIONALE 303 across pre-specified subgroups in a Phase 3 trial of 2L NSCLC at ESMO (Free ESMO Whitepaper) 2022; and
Presented clinical data at 2022 World Conference on Lung Cancer, including final analysis of the global, Phase 3 RATIONALE 303 trial (NCT03358875) with tislelizumab monotherapy compared to chemotherapy in previously treated advanced NSCLC.
Ociperlimab (BGB-A1217), an investigational anti-TIGIT monoclonal antibody with competent Fc function. The global ociperlimab development program includes more than 25 countries and regions, and more than 1,500 subjects have been enrolled.

Presented data from Phase 1 trial (NCT04047862) in combination with tislelizumab in PD-L1 expressing NSCLC at the 2022 World Conference on Lung Cancer (WCLC); and
Presented additional data from Phase 1 cohorts in combination with tislelizumab and chemotherapy in NSCLC at ESMO (Free ESMO Whitepaper) 2022.
BGB-11417, an investigational highly selective and highly potent inhibitor of BCL-2, being developed as monotherapy or in combination with zanubrutinib. The global BGB-11417 development program includes more than 10 countries and regions, and more than 300 subjects have been enrolled.

Initiated patient dosing in Phase 2 study (NCT05471843) to evaluate BCL-2 inhibitor BGB-11417 in patients with relapsed or refractory mantle cell lymphoma.
Initiated patient dosing in BGB-11417-202 study, a single-arm phase 2 study to evaluate BGB-11417 in patients with RR CLL/SLL, conducted in China.
Early-Stage Programs

Initiated patient dosing in the Phase 1 trial (NCT05494762) of BGB-B167, an investigational first-in-class CEA x 4-1BB bispecific antibody, as a monotherapy and in combination with tislelizumab in patients with selected CEA-expressing advanced or metastatic solid tumors, including colorectal cancer (CRC);
Initiated enrollment of surzebiclimab (BGB-A425) an anti-TIM3 antibody in combination with tislelizumab in tumor specific cohorts of NSCLC and head and neck squamous cell carcinoma (HNSCC) (NCT03744468); and
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 in tumor specific cohorts of NSCLC and HNSCC or in combination with tislelizumab in advanced solid tumors;
BGB-15025: an investigational, first-in-class hematopoietic progenitor kinase 1 (HPK1) inhibitor as monotherapy or in combination with tislelizumab in solid tumors;
BGB-16673: an investigational Chimeric Degradation Activating Compound (CDAC), targeting BTK protein degradation as monotherapy in B cell malignancies;
BGB-24714: an investigational Second Mitochondrial-derived Activator of Caspase, or SMAC, mimetic as monotherapy or in combination with paclitaxel in advanced 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; and
BGB-23339: a potent, allosteric investigational tyrosine kinase 2 (TYK2) inhibitor.
Collaboration Programs

In collaboration with Nanjing Leads Biolabs, initiated patient dosing in the BeiGene-sponsored 900-102 clinical trial of LAG3 inhibitor LBL-007 in combination with tislelizumab in advanced solid tumors (NCT03744468).
Manufacturing Operations

Construction continues on the U.S. flagship commercial-stage manufacturing and clinical R&D campus at the Princeton West Innovation Campus in Hopewell, N.J. The property has more than one million square feet of developable real estate for potential future expansion;
Continued construction on our new small molecule manufacturing campus in Suzhou, China. Phase 1 of construction is expected to bring more than 52,000 square meters and expand production capacity to 600 million tablets/capsules and be completed in 2023. Once completed, qualified, and approved, the total production capacity is expected to increase our small molecule manufacturing capability in China by up to a total of ten times capacity; and
Continued construction on our state-of-the-art biologics facility in Guangzhou, China, which currently is approved for 16,000 liters of biologics capacity, with an additional phase of construction to bring total capacity to 54,000 liters expected to be completed and GMP-ready by the end of 2022 and an additional 10,000 liters in the second quarter of 2023.
Corporate Developments

Entered into a strategic alliance with Ontada, a McKesson business with leading provider technology and actionable real-world research, education, and evidence in oncology, to improve U.S. community oncology care through the development of real-world evidence (RWE) data, tools, and insights to help increase access to affordable, cutting-edge therapies.
Expected Milestones

BRUKINSA

Continue to support ongoing FDA review of the sNDA for CLL/small lymphocytic lymphoma, which has a PDUFA target action date of January 2023;
Continue to support the European Medicines Agency (EMA) and European Commission for the approval of new indication applications for CLL;
Continue to support Health Canada review of sNDA for CLL;
Continue to support NMPA review of sNDA for 1L CLL/SLL in China;
Continue to support the review of MHRA and Swissmedic for new indication application for MZL and CLL;
Present final analysis data for the global Phase 3 ALPINE trial (NCT03734016) including progression-free survival at an upcoming medical congress; and
Present key data from BRUKINSA clinical development programs at 64th American Hematology Association Meeting (December 10-14, New Orleans) including an oral presentation for BRUKINSA in MZL (MAGNOLIA trial), and a poster with updated results for BRUKINSA in acalabrutinib-intolerant patients with B-cell malignancies.
Tislelizumab

Continue to support NMPA review of BLA application for tislelizumab in combination with chemotherapy as a 1L treatment for patients with advanced or metastatic gastric or gastroesophageal junction adenocarcinoma whose tumors express PD-L1, and for tislelizumab in combination with chemotherapy as a 1L treatment in patients with unresectable locally advanced, recurrent or metastatic ESCC;
Continue interaction with NMPA for sBLA for tislelizumab as a treatment for 1L hepatocellular carcinoma;
Continue to support review by regulatory authorities of BeiGene’s applications for tislelizumab including: Australia’s TGA review and New Zealand’s Medsafe review of BLA for tislelizumab in 1L/2L NSCLC and 2L ESCC, and South Korea’s MFDS review of BLA for tislelizumab in 2L ESCC;
In collaboration with Novartis, continue to support review of marketing applications including:
Ongoing FDA review of the BLA submission in 2L ESCC including facilitating scheduling the required inspections as soon as possible;
EMA review of marketing authorization applications for tislelizumab in 1L/2L NSCLC and 2L ESCC;
UK MHRA review of tislelizumab for treatment of 1L/2L NSCLC and 2L ESCC in Great Britain via Reliance route;
Swiss Medic review of marketing authorization applications for tislelizumab in 2L ESCC; and
Support U.S. FDA regulatory submission by Novartis in 2023 for 1L gastric cancer, 1L unresectable ESCC, and 1L HCC.
BGB-11417 (BCL-2)

Present Phase 1 clinical data for non-Hodgkin’s lymphoma, CLL, acute myeloid leukemia (AML) and multiple myeloma (MM) (NCT04883957, NCT04277637, NCT04771130, and NCT04973605) at ASH (Free ASH Whitepaper) 2022.
Collaboration Programs

In collaboration with Zymeworks, announce topline results for a Phase 2b clinical trial of zanidatamab in advanced or metastatic HER2-amplified biliary tract cancers (NCT04466891) in 2022.
COVID-19 Impact and Response

We expect that the worldwide health crisis of COVID-19 will continue to have a negative impact on our operations, including commercial sales, regulatory interactions, inspections, filings, manufacturing, and clinical trial recruitment, participation, and data readouts. There remains uncertainty regarding the future impact of the pandemic both globally and specifically in China due to outbreaks and restrictions and potential impact on clinical, manufacturing and commercial operations. We are striving to minimize delays and disruptions, have put protocols and procedures in place, and continue to execute on our commercial, regulatory, manufacturing, and clinical development goals globally.

1 We revised certain prior period financial statements for an error related to the valuation of net deferred tax assets, the impact of which was immaterial to our previously filed financial statements in the first and second quarters of 2022 and the quarterly and annual periods of fiscal 2021 (see "Notes to the Condensed Consolidated Financial Statements, Note 1. Description of Business, Basis of Presentation and Consolidation and Significant Accounting Policies" and "Note 2. Revision of Prior Period Financial Statements" included in our Quarterly Report on Form 10-Q for the period ended September 30, 2022 filed with the SEC).

On November 9, 2022 NanoString Technologies, Inc. (NASDAQ: NSTG), a leading provider of life science tools for discovery and translational research, and Abcam (AIM:ABC; NASDAQ:ABCM), a global life science company working together with researchers to advance science and enable faster breakthroughs, reported the expansion of their long-standing relationship with a new agreement to co-market Abcam antibodies for NanoString’s high-plex spatial multiomic solutions (Press release, Abcam, NOV 9, 2022, View Source [SID1234623565]).

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Under the terms of the agreement, Abcam RabMAb recombinant antibodies will be commercialized as part of the first 64-plex protein panel for NanoString’s CosMx Spatial Molecular Imager (SMI). Jointly developed and validated by NanoString and Abcam, the human immuno-oncology panel is the first on the market to combine high-plex spatial proteomic and transcriptomic analyses at single-cell and subcellular resolution. This provides unprecedented insights into immune cells, tumors and their neighborhood and aims to accelerate immune-oncology research supporting better understanding of clinical response and therapeutic resistance.

"We have partnered with Abcam to facilitate access to their broad portfolio of high-quality, validated antibodies to augment our CosMx protein panels," said Brad Gray, president and CEO of NanoString. "This relationship will further expand the depth and breadth of spatial biology offerings on NanoString instrumentation into new frontiers of human biology down to single-cell resolution— a true revolution in the spatial biology field."

"We are excited to enter a new phase of our relationship with NanoString. For the past six years, our teams have worked together to accelerate the development of novel technologies for the biomarker and clinical research community," said John Baker, SVP of Marketing of Abcam. "We are hopeful that these innovations will unlock the full potential of spatial biology and will ultimately help improve care for people with cancer".

NanoString will be hosting a symposium at the 37th Annual Meeting of the Society of Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Conference (SITC) (Free SITC Whitepaper) on Nov. 10 from 11:40 AM to 1:10 PM EST and will highlight the CosMx protein capability co-developed with Abcam. In the coming months NanoString and Abcam will co-host webinars and events to share insight on spatial biology in immuno-oncology and other applications such as neuroscience.