On August Arcus Biosciences, Inc. (NYSE:RCUS), a clinical-stage, global biopharmaceutical company focused on developing differentiated molecules and combination therapies for people with cancer, reported that Dimitry S.A. Nuyten, M.D., Ph.D has been appointed chief medical officer (CMO) effective August 1, 2022 (Press release, Arcus Biosciences, AUG 8, 2022, View Source [SID1234617818]). In his role as CMO, Dr. Nuyten will oversee Arcus’s clinical development organization that includes nearly 200 employees and six clinical-stage programs targeting TIGIT, the adenosine axis (CD73 and dual A2a/A2b), HIF-2a and PD-1. Dr. Nuyten will oversee the advancement of four registrational Phase 3 trials that are ongoing or expected to start by year end for the anti-TIGIT antibody domvanalimab in novel combinations across multiple cancers.

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"Dr. Nuyten’s attributes and experiences are well matched to Arcus’s rapid evolution as we enter 2023 with four ongoing registrational trials for domvanalimab-based combinations and a portfolio of Phase 2 and early signal-seeking trials investigating combinations of our six clinical molecules," said Terry Rosen, Ph.D., chief executive officer of Arcus. "His proven abilities to grow and lead large cross-functional teams, interface with commercial and regulatory organizations and navigate complex portfolio management will complement our exceptional development organization and facilitate the continued growth of Arcus. In Dr. Nuyten’s new role, he will also be working closely with our global partners, including Gilead Sciences, to optimize and implement our clinical development strategy."

As part of his role as CMO, Dr. Nuyten will serve as a member of Arcus’s executive committee and co-chair of Arcus’s and Gilead’s Joint Steering Committee. He will be responsible for our clinical organization, including clinical development and operations, clinical pharmacology and biometrics. Prior to joining Arcus, Dr. Nuyten served as senior vice president and CMO of Nektar Therapeutics where he led a 200-person development organization which included clinical development, safety, clinical operations, medical affairs, clinical and non-clinical pharmacology, biostats, data management and programming. Prior to Nektar, he served as CMO of Aduro Biotech and served as the immuno-oncology development leader and vice president of global product development for oncology at Pfizer, where he led the late-stage development of Bavencio and early-stage clinical programs for oncology and immune-oncology. Prior to Pfizer, Dr. Nuyten was group medical director at BristolMyers Squibb. He holds a Ph.D. in cancer biology from the University of Amsterdam Medical School in The Netherlands, is Board Certified in radiation oncology and certified as a physician in The Netherlands by the University of Groningen Medical School. Over the course of his career, Dr. Nuyten has authored numerous peer-reviewed papers, is co-inventor on multiple patents and has been recognized with prestigious awards, including as a two-time recipient of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Merit Award.

"My career has been dedicated to understanding and exploiting the biologic drivers of cancer to develop new treatments that have the potential to improve outcomes or even cure cancer," said Dimitry Nuyten, M.D., Ph.D, incoming chief medical officer at Arcus Biosciences. "I was attracted to Arcus by the breadth and diversity of its portfolio of molecules and clinical programs and the corresponding opportunity to substantially impact the way that many important cancers are treated. I am thrilled to join the company and excited to work with the talented and patient-centric Arcus team to translate an innovative pipeline into clinically meaningful therapies for a broad array of cancers with high unmet medical need."

Arcus Ongoing and Announced Clinical Studies

Trial Name

Arms

Setting

Status

NCT No.

Lung Cancer

ARC-7

zim vs. dom + zim vs. etruma + dom + zim

1L NSCLC (PD-L1 ≥ 50%)

Ongoing Randomized Phase 2

NCT04262856

PACIFIC-8

(AZ)

dom + durva vs. durva

Curative-Intent Stage 3 NSCLC

Ongoing Registrational Phase 3

NCT05211895

ARC-10

dom + zim vs. zim vs. chemo

1L NSCLC (PD-L1 ≥ 50%)

Ongoing Registrational Phase 3

NCT04736173

STAR-121

(GILD)

dom + zim + chemo vs pembro + chemo

1L NSCLC (PD-L1 all-comers)

Planned Registrational Phase 3

TBD

EDGE-Lung

dom + zim +/- quemli

1L/2L NSCLC (lung cancer platform study)

In Planning Phase 2

TBD

Lung Platform (GILD)

dom + zim +/- etruma or sacituzumab govitecan (Trodelvy) or other combos

1L/2L NSCLC (lung cancer platform study)

In Planning Phase 2

TBD

Gastrointestinal Cancers

ARC-9

etruma + zim + mFOLFOX vs. SOC

2L/3L/3L+ CRC

Ongoing

Randomized Phase 2

NCT04660812

ARC-21

dom + zim ± chemo

1L/2L Upper GI Malignancies

Ongoing

Phase 2

NCT05329766

STAR-221

dom + zim + chemo vs. nivo + chemo

GI Malignancies

Planned Registrational Phase 3

TBD

Pancreatic Cancer

ARC-8

quemli + zim + gem/nab-pac vs. quemli + gem/nab-pac

1L, 2L PDAC

Ongoing Randomized Phase 1/1b

NCT04104672

Prostate Cancer

ARC-6

etruma + zim + SOC vs. SOC (Adding sacituzumab govitecan (Trodelvy) combination cohorts)

2L/3L CRPC

Ongoing Randomized Phase 2

NCT04381832

Various

ARC-12

AB308 + zim

Advanced Malignancies

Ongoing

Phase 1/1b

NCT04772989

ARC-14

AB521

Healthy Volunteers

Ongoing

NCT05117554

ARC-20

AB521

Cancer Patients / ccRCC

Planned Phase 1/1b

TBD

dom: domvanalimab; durva: durvalumab; etruma: etrumadenant; gem/nab-pac: gemcitabine/nab-paclitaxel; nivo: nivolumab; pembro: pembrolizumab; quemli: quemliclustat; SOC: standard of care; zim: zimberelimab; ccRCC: clear-cell renal cell carcinoma

About the Gilead Collaboration

In May 2020, Gilead and Arcus entered into a 10-year collaboration that provided Gilead immediate rights to zimberelimab and the right to opt into all other Arcus programs arising during the collaboration term. In November 2021, Gilead and Arcus amended the collaboration in connection with Gilead’s option exercise for three of Arcus’s then-clinical stage programs. For all other programs that are in clinical development or new programs that enter clinical development thereafter, the opt-in payments are $150 million per program. Gilead’s option, on a program-by-program basis, expires after a specified period of time following the achievement of a development milestone for such program and Arcus’s delivery to Gilead of the requisite qualifying data package. Concurrent with the May 2020 collaboration agreement, Gilead and Arcus entered into a stock purchase agreement under which Gilead made a $200 million equity investment in Arcus. That stock purchase agreement was amended and restated in February 2021 in connection with Gilead’s increased equity stake in Arcus from 13% to 19.5%, with an additional $220 million investment.

Gilead and Arcus are co-developing and equally share global development costs for five clinical candidates, including domvanalimab, an Fc-silent anti-TIGIT antibody, etrumadenant, a dual adenosine A2a/A2b receptor antagonist, quemliclustat, a small molecule inhibitor of CD73, and zimberelimab, an anti-PD1 antibody.

On August 8, 2022 Guardant Health, Inc. (Nasdaq: GH), a leading precision oncology company, reported it will be participating in the upcoming UBS Genomics 2.0 and MedTech Innovations Summit Conference in Dana Point, CA (Press release, Guardant Health, AUG 8, 2022, View Source [SID1234617817]).

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Guardant Health’s management is scheduled to participate in a fireside chat on Wednesday, August 10 at 2:00 p.m. Pacific Time / 5:00 p.m. Eastern Time. Interested parties may access a live and archived webcast of the presentation on the "Investors" section of the company website at: www.guardanthealth.com.

On August 8, 2022 Scholar Rock (NASDAQ: SRRK), a Phase 3 clinical-stage biopharmaceutical company focused on the treatment of serious diseases in which protein growth factors play a fundamental role, reported financial results and corporate updates for the second quarter ended June 30, 2022 (Press release, Scholar Rock, AUG 8, 2022, View Source [SID1234617816]).

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"We are pleased to have reported important progress with our two clinical programs during the second quarter. Enrollment continues to advance in our pivotal Phase 3 SAPPHIRE trial for apitegromab in SMA. We also presented new data from our Phase 2 TOPAZ trial highlighting sizeable and sustained improvement in Hammersmith Functional Motor Scale-Expanded (HFMSE) scores at 24 months for non-ambulatory patients, reinforcing our belief in the unique potential of apitegromab as a muscle-targeted therapy to treat SMA, and we continue to evaluate these patients in their third year of treatment," said Nagesh Mahanthappa, Founding Chief Executive Officer & President of Scholar Rock. "In our SRK-181 program, enrollment is ongoing in the Phase 1 DRAGON trial Part B dose expansion. We look forward to providing updates on DRAGON as data become available. Further, our focused research continues to make excellent progress as we develop next-generation programs to build out our future pipeline."

Company Highlights and Upcoming Milestones

Apitegromab is a selective inhibitor of myostatin activation being developed as the first muscle-targeted therapy with the potential to treat spinal muscular atrophy (SMA).

Positive 24-Month Phase 2 TOPAZ Extension Data Support Potential Benefit for Patients. Scholar Rock announced positive data at the Cure SMA Research & Clinical Care Meeting in June, demonstrating sizable and sustained motor function improvement at 24 months with apitegromab as measured by Hammersmith Functional Motor Scale-Expanded (HFMSE) scores for non-ambulatory patients with Types 2 and 3 SMA on nusinersen. Results also showed a substantial increase in Revised Upper Limb Module (RULM) scores, with no serious safety risks identified over 24 months of apitegromab treatment. Of the 55 patients who completed the 24-month extension period, 54 opted to continue into the 36-month extension period.
Enrollment Ongoing for Phase 3 SAPPHIRE Clinical Trial Evaluating Apitegromab in Non-Ambulatory Patients with Types 2 and 3 SMA. The randomized, double-blind, placebo-controlled Phase 3 clinical trial is evaluating apitegromab for patients on either nusinersen or risdiplam. Approximately 156 non-ambulatory patients aged 2-12 years old with Types 2 and 3 SMA are planned to be enrolled in the main efficacy population. Patients will be randomized 1:1:1 to receive for 12 months either apitegromab 20 mg/kg, apitegromab 10 mg/kg, or placebo by intravenous (IV) infusion every 4 weeks. SAPPHIRE is expected to be conducted across 55 sites in the U.S. and Europe. Scholar Rock presented on the trial design at the 17th International Congress on Neuromuscular Diseases (ICNMD 2022) in July 2022, along with publication of the abstract in the peer-reviewed Journal of Neuromuscular Diseases.
SRK-181 is a selective inhibitor of latent TGFβ1 activation being developed with the aim of overcoming primary resistance to and increasing the number of patients who may benefit from checkpoint inhibitor therapy.

Advancing Enrollment for Part B of the Phase 1 DRAGON Proof-of-Concept Clinical Trial for SRK-181. Part B of the Phase 1 DRAGON trial consists of multiple proof-of-concept cohorts focused on evaluating the ability of SRK-181 to overcome primary resistance to anti-PD-(L)1 therapy in patients with solid tumors. The biomarker strategy for DRAGON explores early signs of SRK-181 activity, including target engagement and pathway modulation. It includes measuring effects on both circulating and tumor immune contexture, such as CD8+ T cell infiltration and reductions in myeloid-derived suppressor cell (MDSC) populations, as well as analysis of TGFβ-related pathway signaling. Initial evidence of drug activity and safety data are anticipated in 2022.
Scholar Rock’s preclinical discovery pipeline includes a highly selective, context-dependent TGFβ1 antibody that inhibits proTGFβ1 activation selectively in the extracellular matrix via targeting the covalent complexes of proTGFβ1 with latent TGFβ binding proteins 1 and 3 ("LTBPs"— the targets are collectively referred to as "LTBP-TGFβ1").

Preclinical Data Supports Selective Targeting of Matrix-Associated TGFβ1 as an Attractive Approach for Anti-Fibrotic Therapy. Scholar Rock recently presented data on its targeted approach to LTBP-TGFβ1 that show reduction of TGFβ1 signaling and reduction of fibrosis in relevant preclinical in vivo models.
Second Quarter 2022 Financial Results

For the quarter ended June 30, 2022, net loss was $44.0 million or $1.06 per share compared to a net loss of $30.7 million or $0.84 per share for the quarter ended June 30, 2021.

Revenue was $0 for the quarter ended June 30, 2022, compared to $4.6 million for the quarter ended June 30, 2021.
Research and development expense was $32.1 million for the quarter ended June 30, 2022, compared to $25.6 million for the quarter ended June 30, 2021. The increase was primarily attributable to increased clinical costs associated with apitegromab and higher personnel costs, including severance expenses associated with the recent restructuring.
General and administrative expense was $11.1 million for the quarter ended June 30, 2022, compared to $9.3 million for the quarter ended June 30, 2021. The increase was primarily due to higher personnel costs, including severance expenses associated with the recent restructuring.
As of June 30, 2022, Scholar Rock had cash, cash equivalents, and marketable securities of approximately $371 million, which is expected to fund the Company’s anticipated operating and capital expenditure requirements into 2025.
"We were thrilled to announce the completion of a $205 million registered direct offering during the quarter. This financing included several high-quality, long-term oriented, fundamentals-based biotechnology investors who saw the promise of our platform and our programs. Importantly, this capital puts us in a strong financial position to fully fund the Phase 3 SAPPHIRE trial, continue advancing Part B of the Phase 1 DRAGON trial for SRK-181, while investing in selected early-stage programs that exemplify the power of our scientific platform," said Ted Myles, Chief Operating Officer and Chief Financial Officer of Scholar Rock.

On August 8, 2022 Foundation Medicine, Inc., Flatiron Health, and Genentech, members of the Roche Group, in partnership with a network of community oncology practices, reported new research in the Journal of Thoracic Oncology Clinical and Research Reports on tumor profiling results from the ongoing, multicenter Prospective Clinicogenomic (PCG) Study (NCT04180176) (Press release, Foundation Medicine, AUG 8, 2022, View Source [SID1234617815]). In this investigation, researchers compared the ability of FoundationOneCDx and FoundationOneLiquid CDx comprehensive genomic profiling (CGP) to limited tissue testing in detecting actionable, guideline-recommended biomarkers for targeted treatment planning in patients with advanced non-squamous non-small cell lung cancer (aNSCLC).

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Despite continued adoption of CGP, most patients with advanced cancer still receive limited biomarker testing. The tumor profiling data from a diverse group of 515 aNSCLC patients in the PCG study demonstrates the superiority of both tissue- and blood-based CGP over more limited tissue testing in detecting actionable biomarkers. Additionally, the findings reinforce the value of blood-based CGP as a compelling and convenient complement to tissue-based CGP, especially when an adequate tissue sample is not immediately available.

Nine genes recommended for testing by clinical guidelines were included in the analysis: EGFR, KRAS, ALK, ROS1, RET, BRAF, MET exon 14, NTRK, as well as emerging biomarkers ERBB2 mutations and MET amplification. At study enrollment, patients with non-squamous aNSCLC received Foundation Medicine’s liquid biopsy CGP testing, and a subset also received Foundation Medicine tissue testing. Results demonstrate that tissue-based FoundationOneCDx and blood-based FoundationOneLiquid CDx both provided superior biomarker detection over more limited tissue testing of up to 5 biomarkers. In particular, Foundation Medicine’s liquid biopsy test detected guideline-recommended biomarkers in 48 additional patients who received single biomarker or hotspot testing.

"Precision oncology is transforming the way patients with cancer are treated, and there has been an explosion of targeted therapy options in lung cancer specifically," said Foundation Medicine’s Chief Medical Officer, Dr. Mia Levy. "With the amount of diverse diagnostic tools now available to physicians, a key clinical question is how to piece these diagnostics together to optimally identify precision treatment options for patients with advanced cancer. Results from this research reinforce the unique benefits, and complementary value of both tissue- and blood-based CGP tests, depending on the patient’s tissue availability, health status and tumor type."

Results from this research reinforce that, in certain patient cases where an adequate tissue sample is immediately available, tissue CGP offers the most reliable detection of guideline-recommended biomarkers. In cases where tissue is not immediately available, blood-based CGP can be used for expeditious CGP testing, though reflex tissue testing may be beneficial if blood-based CGP does not detect an actionable alteration to inform therapy selection. An important reason for this distinction is that liquid biopsy sensitivity is dependent upon the amount of tumor shed into the blood stream, called circulating tumor DNA (ctDNA). When ctDNA shed for a patient is low, a blood-based test may not be able to detect the ctDNA in the blood and tissue testing could yield additional insights.

"This initial analysis of the PCG Study data provides meaningful insights to help oncologists select the appropriate molecular diagnostic platform for their patients with lung cancer," said Dr. Neal Meropol, Vice President, Research Oncology and Scientific and Clinical Lead, Clinical Research, Flatiron Health. "This research reinforces how advances in precision oncology are benefitting patients with advanced non-small cell lung cancer."

The PCG Study, funded and sponsored by Genentech, pilots the use of a technology-enabled prospective data collection platform to facilitate, streamline and simplify the execution of clinical trials for patients living with advanced lung cancer, and secondarily aims to better understand how genomic changes in a patient’s tumor may predict response or impact resistance to treatment. A complete report of the PCG Study will be forthcoming to more fully describe the genomics of the pre-treatment and on-treatment comprehensive genomic profiling and its relationship to patient outcomes.

On August 8, 2022 Pyramid Biosciences, Inc., a Boston-based, clinical-stage biotechnology company focused on developing new and highly differentiated precision therapies for cancer and other serious diseases, reported the expansion of its senior leadership team (Press release, Pyramid Biosciences, AUG 8, 2022, View Source [SID1234617814]). Nushmia Khokhar, MD has joined the company as Chief Medical Officer, where she will oversee the advancement and expansion of the Company’s clinical pipeline.

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"Dr. Khokhar has a proven track record of successfully bringing novel oncology compounds through clinical development to global approval," said CEO of Pyramid Biosciences, Brian Lestini, MD, PhD. "We are looking forward to Dr. Khokhar’s leadership of our clinical programs during this important growth stage of our company."

Prior to joining Pyramid Biosciences, Dr. Khokhar served as Chief Medical Officer at Umoja Biopharma, a multi-platform, immuno-oncology company based in Seattle, WA. In this capacity, Dr. Khokhar oversaw Umoja’s clinical development, operations, and regulatory functions. Prior to joining Umoja, Dr. Khokhar was the Senior Vice President & Head of Clinical Development at Autolus Therapeutics, where she played a critical role in advancing the company’s autologous CAR T-cell products and clinical programs. Prior to that, Dr. Khokhar held numerous roles at Janssen Oncology, a subsidiary of Johnson & Johnson (NYSE: JNJ) where she led several successful clinical trials, directed the Phase 3 registration trial of trabectedin (YONDELIS) in soft tissue sarcomas, and served as the Global Clinical Leader for the breakthrough therapy daratumumab (DARZALEX) for hematologic cancers.

"I look forward to working with the outstanding team at Pyramid Biosciences, progressing the Company’s promising therapies through clinical development and building a robust pipeline," said Dr. Khokhar.

"We are extremely pleased to have Nushmia join our senior leadership team as we continue to grow our clinical programs and develop new medicines for underserved patients," said Jordan Leef, Pyramid Biosciences’ Co-Founder & COO.

Dr. Khokhar is a graduate of Aga Khan University and completed her post-doctoral fellowship at Memorial Sloan-Kettering Cancer Center, where she focused on pharmacology and molecular therapeutics. Following her post-doctoral fellowship, Dr. Khokhar completed a residency in internal medicine at Washington Hospital Center and a fellowship in Hematology/Oncology at the Northwestern University Hospital. Dr. Khokhar is board certified in medical oncology.