On August 9, 2022 Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, reported financial results for the second quarter ended June 30, 2022 (Press release, Cogent Biosciences, AUG 9, 2022, View Source [SID1234617861]).

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"In the second quarter we achieved a number of important milestones as we continued to advance bezuclastinib and grow the research and development pipeline," said Andrew Robbins, President and CEO of Cogent Biosciences. "Most notably, we reported positive initial clinical data from our APEX trial that strengthened our belief in bezuclastinib’s potential to provide meaningful clinical activity for systemic mastocytosis patients, without the tolerability challenges seen with other available treatment options. We remain on track to provide another clinical update from this trial by the end of 2022. We are equally excited about the opportunity with bezuclastinib in non-advanced systemic mastocytosis and gastrointestinal stromal tumor (GIST) patients and expect to provide clinical data updates on these programs during the first half of 2023. Based on the positive APEX data, we were able to secure additional financing at the end of the quarter, and we are confident this will support our go forward strategy into 2025."

Recent Business Highlights

In June 2022, Cogent reported positive initial data from its ongoing Phase 2 APEX clinical trial evaluating the selective KIT D816V inhibitor, bezuclastinib, in patients with advanced systemic mastocytosis (AdvSM).
As of the data cutoff date, May 24, 2022, all 11 patients treated were evaluated for signs of clinical activity. Bezuclastinib demonstrated rapid reductions in serum tryptase, with all patients achieving a ≥50% reduction (10/11 achieved within the first week of treatment) and 6/11 achieving serum tryptase <20ng/mL. All patients remained on treatment with treatment duration ranging from 0.5 – 4.8 months. Bezuclastinib was generally well-tolerated at all doses with no reported periorbital or peripheral edema, cognitive effects or intracranial bleeding events.
In April 2022, the Company presented early data and outlined its strategy to create best-in-class small molecules from the company’s growing pipeline of novel, targeted therapy programs at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) annual meeting and company sponsored R&D investor event.
Announced plans to advance a potent, selective FGFR2 inhibitor toward candidate selection with a product profile that includes best-in-class selectivity against all known FGFR2 primary driver and secondary resistance mutations.
Announced development of an ErbB2 mutant selective inhibitor for patients with mutations that are not well addressed by therapies currently approved or in clinical development.

Appointed Fang Fang, Ph.D., Vice President, Biometrics in Development Operations.

Dr. Fang joins Cogent with over 20 years of industry experience and leadership in oncology biometrics and biostatistics. Prior to joining, she was Vice President, Biometrics at Kiniksa Pharmaceuticals. Earlier in her career, Dr. Fang held roles of increasing responsibility at Merrimack Pharmaceuticals, Bayer Healthcare, Eisai Medical Research and Astellas Pharma. Dr. Fang received her Ph.D. in Biostatistics from Rutgers University.
Upcoming Milestones

Present additional data from APEX, a global, multicenter Phase 2 clinical trial of bezuclastinib in patients with advanced systemic mastocytosis (AdvSM) by the end of 2022.

Present initial data from SUMMIT, a randomized, double-blind, placebo-controlled, global, multicenter, Phase 2 clinical trial with bezuclastinib for nonadvanced systemic mastocytosis (NonAdvSM) in the first half of 2023.

Present lead-in data from PEAK, a registrational randomized, open-label, global, Phase 3 clinical trial in patients with gastrointestinal stromal tumors (GIST), in the first half of 2023.

File first internally developed Investigational New Drug application (IND) from Cogent’s potent, selective FGFR2 inhibitor program in the second half of 2023.

Second Quarter 2022 Financial Results

Cash Position: As of June 30, 2022, cash and cash equivalents were $325.6 million, as compared to $191.0 million as of March 31, 2022. The company believes that its cash and cash equivalents will be sufficient to fund its operating expenses and capital expenditure requirements into 2025.

R&D Expenses: Research and development expenses were $29.5 million for the second quarter of 2022 as compared to $12.4 million for the second quarter of 2021. The increase was primarily due to costs associated with the on-going APEX, SUMMIT and PEAK clinical trials and costs related to expanding the Cogent Research Team, which was formed in the second quarter of 2021. R&D expenses include non-cash stock compensation expense of $2.1 million for the second quarter of 2022 compared to $1.0 million for the second quarter of 2021.

G&A Expenses: General and administrative expenses were $6.4 million for the second quarter of 2022 as compared to $4.9 million for the second quarter of 2021. The increase was primarily due to the growth of the organization. G&A expenses include non-cash stock compensation expense of $2.4 million for the second quarter of 2021 compared to $1.6 million for the second quarter of 2021.

Net Loss: Net loss was $34.9 million for the second quarter of 2022 as compared to a net loss of $16.5 million for the same period of 2021.

On August 9, 2022 Avidity Biosciences, Inc. (Nasdaq: RNA), a biopharmaceutical company committed to delivering a new class of RNA therapeutics called Antibody Oligonucleotide Conjugates (AOCs), reported financial results for the second quarter ended June 30, 2022 and highlighted recent corporate progress (Press release, Avidity Biosciences, AUG 9, 2022, View Source [SID1234617906]).

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"We are very pleased with the team’s execution on our ambitious goal of having three AOC programs addressing three distinct rare diseases in the clinic by the end of this year," said Sarah Boyce, president and chief executive officer. "Our AOC 1001 program for DM1 is progressing with patients from the MARINA trial now enrolling in the recently initiated MARINA-OLE trial. We remain on track to report a preliminary assessment from MARINA in the fourth quarter. We also continue to collaborate with the FSHD and DMD communities as we work to advance AOC 1020 and AOC 1044 into the clinic by the end of this year."

"Our strong cash balance of over $400 million, inclusive of additional funds raised subsequent to June 30th, positions us to be well funded through 2024. This allows us to meaningfully advance our DM1, FSHD and DMD programs, as well as other programs in skeletal muscle and expand the platform into other tissues and cell types," said Mike MacLean, chief financial and chief business officer.

Recent Highlights
Commenced enrolling patients from the MARINA study into a Phase 2 open-label extension study (MARINA-OLE) of AOC 1001 in adults with DM1. Click here for more information on the MARINA-OLE or visit www.clinicaltrials.gov and search for NCT05479981.
Presented data supporting Avidity’s approach of directly targeting DUX4 with AOC 1020 at the 29th Annual FSHD Society International Research Congress. Key highlight from the conference:
Data from a FSHD mouse model showed that a single intravenous dose with the murine version of AOC 1020 prevented development of muscle weakness demonstrated by three functional assays – treadmill running, in vivo force and compound muscle action potential.
Second Quarter 2022 Financial Results
Cash, Cash Equivalents and Marketable Securities: Cash, cash equivalents and marketable securities totaled $398.2 million as of June 30, 2022, compared to $405.5 million as of December 31, 2021. In addition, subsequent to June 30th, we have raised $18.7 million through our "at the market" program.

Collaboration Revenue: Collaboration revenue, including reimbursable expenses, primarily relates to Avidity’s partnership with Eli Lilly and Company (Lilly) and totaled $2.2 million for the second quarter of 2022 compared with $2.6 million for the second quarter of 2021, and $4.0 million for the first six months of 2022 compared with $5.3 million for the first six months of 2021. The decrease was primarily due to timing of reimbursable collaboration-related research and development expenses resulting in the recognition of lower corresponding revenue under the collaboration with Lilly.

Research and Development (R&D) Expenses: R&D expenses include external and internal costs associated with research and development activities. These expenses were $39.8 million for the second quarter of 2022 compared with $22.7 million for the second quarter of 2021, and $67.5 million for the first six months of 2022 compared with $43.4 million for the first six months of 2021. The increase was primarily driven by the advancement of AOC 1001, AOC 1020 and AOC 1044, as well as internal and external costs related to the expansion of the company’s overall research capabilities.

General and Administrative (G&A) Expenses: G&A expenses primarily consist of employee-related expenses, professional fees, insurance costs, and patent filing and maintenance fees. These expenses were $8.7 million for the second quarter of 2022 compared with $6.3 million for the second quarter of 2021, and $17.3 million for the first six months of 2022 compared with $12.2 million for the first six months of 2021. The increase was primarily due to higher personnel costs and professional fees as well as facilities costs to support the company’s expanded operations.

On August 9, 2022 Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, reported financial results for the second quarter of 2022 (Press release, Oncternal Therapeutics, AUG 9, 2022, View Source [SID1234617922]).

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"The second quarter of 2022 was highlighted by an encouraging data update at ASCO (Free ASCO Whitepaper) from our Phase 1/2 study of zilovertamab plus ibrutinib in patients with MCL and CLL. We were especially excited by the results in MCL and CLL patients with loss of p53 function, which is a challenging population to treat with current standard of care BTK inhibitor monotherapy" said James Breitmeyer, M.D., Ph.D., Oncternal’s President and CEO. "We are now looking forward to critical near-term catalysts for the company, including the planned initiation of our Phase 3 Study ZILO-301, the submission of our IND for the first-in-human study of ONCT-808, our ROR1-targeting CAR expressing T cell therapy candidate, and the further advancement towards the clinic of ONCT-534, our Dual-Acting Androgen Receptor Inhibitor (DAARI) product candidate that may address key resistance mechanisms in metastatic prostate cancer. All this is underpinned by focused execution and prudent cash and resource management. We currently expect our cash runway will last into the first half of 2024."

Recent Highlights

In June 2022, we announced an interim clinical data update from the ongoing Phase 1/2 clinical trial of zilovertamab in combination with ibrutinib for patients with mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL) [NCT03088878] at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2022 Annual Meeting:
Objective response rate (ORR) of 85% (23 of 27 evaluable patients) observed for patients with MCL treated with zilovertamab plus ibrutinib, which compares favorably to the historical ORR of 66% for ibrutinib monotherapy
Complete response (CR) rate of 41% for patients with MCL treated with zilovertamab plus ibrutinib (11 of 27 evaluable patients), which compares favorably to the historical ORR of 20% for ibrutinib monotherapy
Median progression-free survival (PFS) of 35.9 months for patients with MCL treated with zilovertamab plus ibrutinib at a median follow-up of 15.1 months, which compares favorably to the historical ibrutinib monotherapy median PFS of 12.8 months
In patients with MCL harboring mutated p53, median PFS of 17.3 months (95% CI: 2.9, NE), which compares favorably to the historical median PFS of 4.0 months (95% CI: 2.1, 8.3) for ibrutinib monotherapy
In patients with p53 pathway-deficient CLL, landmark PFS with zilovertamab plus ibrutinib of 100% at 24 months and 100% at 30 months, which compare favorably to the historical ibrutinib monotherapy landmark PFS of ~68% and ~55% at 24 months and 30 months, respectively. Mutations in or loss of p53 protein, which has been called the "guardian of the genome," is a well-known negative factor in many types of cancer, through genomic instability and loss of tumor suppression
The combination of zilovertamab and ibrutinib continued to be well tolerated, with a safety profile consistent with or improved compared with historical data for ibrutinib monotherapy
In June 2022, we established a clinical trial collaboration and supply agreement with Pharmacyclics, which includes the supply of ibrutinib to support our global registrational Phase 3 study ZILO-301, to treat patients with relapsed or refractory MCL with zilovertamab plus ibrutinib.
In April 2022, a Phase 1b investigator sponsored trial of zilovertamab plus docetaxel for patients with metastatic castration-resistant prostate cancer (mCRPC) was initiated at the University of California, San Diego.
In April 2022, we established a clinical manufacturing agreement with the Dana-Farber Cancer Institute to conduct cGMP cell preparation and manufacturing activities for use in first-in-human studies of our ROR1-targeting CAR-T cell therapy candidate ONCT-808.
Expected Upcoming Milestones

Zilovertamab, our ROR1 antibody program
Initiation of global registrational Phase 3 Study ZILO-301, in September 2022
Interim clinical data update for patients with MCL and CLL treated with zilovertamab plus ibrutinib in ongoing Phase 1/2 clinical study CIRM-0001, in the fourth quarter of 2022
ONCT-808, lead candidate in our autologous ROR1-targeted CAR-T cell therapy program
Investigational New Drug (IND) application submission in August 2022
ONCT-534, lead candidate in our DAARI program
FDA pre-IND interactions in the fourth quarter of 2022
Second Quarter 2022 Financial Results
Our grant revenue was $0.2 million for the second quarter ended June 30, 2022. Our grant revenue is derived from a subaward under a grant from the California Institute for Regenerative Medicine (CIRM) to the University of California, San Diego and two research and development grant awards from the National Institutes of Health (NIH).

Our total operating expenses for the second quarter ended June 30, 2022 were $12.0 million, including $1.7 million in non-cash stock-based compensation expense. Research and development expenses for the quarter totaled $8.8 million, and general and administrative expenses for the quarter totaled $3.2 million. Net loss for the second quarter was $11.7 million, or a loss of $0.23 per share, basic and diluted.

As of June 30, 2022, we had approximately 52.2 million shares of common stock outstanding, $78.9 million in cash and cash equivalents and no debt. We believe these funds will be sufficient to fund our operations into the first half of 2024. Our cash guidance is subject to a number of assumptions, including those related to the severity and duration of the COVID-19 pandemic, and the pace of our research and clinical development programs, among other aspects of our business and the geopolitical environment.

On August 9, 2022 BeiGene (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global biotechnology company focused on developing innovative and affordable oncology medicines to improve treatment outcomes and access for patients worldwide, reported that the global Phase 3 RATIONALE 301 trial with tislelizumab met its primary endpoint of non-inferior Overall Survival (OS) versus sorafenib as a first-line treatment in adult patients with unresectable hepatocellular carcinoma (HCC) (Press release, BeiGene, AUG 9, 2022, View Source [SID1234617938]). The safety profile for tislelizumab was consistent with previous studies and no new safety signals were reported. More than 600 patients in the U.S., Europe, and Asia participated in the study.

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HCC is the sixth most common type of cancer worldwide, accounting for more than 900,000 new cases in 2020i, and despite improvements in screening, surveillance rules, and imaging, more than two-thirds of patients with HCC present with advanced disease at diagnosisii.

"Patients with unresectable HCC face a devastating prognosis, with a median life expectancy of one year. Currently there are few treatment options if patients cannot tolerate TKI therapy or if their condition progresses," said Mark Lanasa M.D., Ph.D., Chief Medical Officer, Solid Tumors at BeiGene. "We are encouraged by the outcome of the final analysis of RATIONALE 301 and look forward to sharing the full safety and efficacy results at an upcoming medical conference."

RATIONALE 301 (NCT03412773) is a global, Phase 3, randomized, open-label study of tislelizumab compared with sorafenib as a first-line treatment in adult patients with unresectable HCC. The primary endpoint of the study is non-inferiority of OS between the two treatment groups. The key secondary endpoint is Overall Response Rate, as assessed by Blinded Independent Review Committee (BIRC) per RECIST v1.1. Other secondary endpoints include other efficacy assessments such as Progression-Free Survival, Durability of Response, and Time to Progression per BIRC, as well as measures of health-related quality of life, and safety and tolerability.

About Tislelizumab

Tislelizumab is a humanized IgG4 anti-PD-1 monoclonal antibody specifically designed to minimize binding to Fc-gamma (Fcγ) receptors on macrophages, helping to aid the body’s immune cells to detect and fight tumors. In pre-clinical studies, binding to Fcγ receptors on macrophages has been shown to compromise the anti-tumor activity of PD-1 antibodies through activation of antibody-dependent macrophage-mediated killing of T effector cells.

Tislelizumab is the first drug from BeiGene’s immuno-oncology biologics program and is being developed internationally as a monotherapy and in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers.

The global tislelizumab clinical development program includes more than 11,000 subjects enrolled to-date in 30 countries and regions. BeiGene has initiated or completed 22 registration-enabling clinical trials. More information on the clinical trial program for tislelizumab can be found here.

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 mono- and combination therapies prioritized in our research and development. BeiGene currently has three approved medicines discovered and developed in our own labs: BTK inhibitor BRUKINSA in the U.S., China, the European Union, Great Britain, Canada, Australia, and additional international markets; and the non-FC-gamma receptor binding anti-PD-1 antibody, tislelizumab, as well as the 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 with 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-PD1 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.

Exelixis has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission .

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