On September 20, 2021 Mirati Therapeutics, Inc. (NASDAQ: MRTX), a clinical-stage targeted oncology company, reported positive topline results from the potentially registration-enabling cohort of the Phase 2 KRYSTAL-1 study, evaluating adagrasib in patients with advanced non-small cell lung cancer (NSCLC) harboring the KRASG12C mutation following prior systemic therapy (Press release, Mirati, SEP 20, 2021, View Source [SID1234588009]).

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The analysis was completed in the intent-to-treat population, which showed adagrasib 600mg BID demonstrated an objective response rate (ORR) of 43% and a disease control rate of 80%, based on central independent review as of June 15, 2021. The median follow-up was 9 months. Importantly, 98.3% of patients received adagrasib following treatment with immunotherapy and chemotherapy. The safety and tolerability profile was consistent with previously reported findings for adagrasib in patients with advanced NSCLC.

The Company plans to submit detailed results from the ongoing Phase 2 registration-enabling cohort of the KRYSTAL-1 study in previously-treated patients with KRASG12C-mutated NSCLC for presentation at a medical congress in early 2022.

"The KRAS mutation has historically been challenging to target, leaving patients with limited treatment options," said Charles M. Baum, M.D., Ph.D., president and chief executive officer, Mirati Therapeutics, Inc. "These positive topline data further strengthen our belief in adagrasib as a potentially differentiated therapy for patients with non-small cell lung cancer harboring the KRASG12C mutation. We look forward to submitting our New Drug Application to the U.S. Food and Drug Administration in the fourth quarter of 2021 and advancing our expanding adagrasib development program, which includes numerous monotherapy and combination studies in KRASG12C-mutated solid tumors."

Updated Findings from Phase 1/1b NSCLC Cohort of KRYSTAL-1 Study

In addition to these topline Phase 2 results, the Company reported updated findings from the Phase 1/1b KRYSTAL-1 study evaluating adagrasib 600mg BID in all 19 patients enrolled with KRASG12C-mutated advanced NSCLC as of the June 15, 2021 data cutoff.

Results showed that the investigator assessed ORR was 58%. Two of the 11 responses occurred in patients after being on treatment for more than 10 months. The median follow-up was 17.3 months. The median duration of treatment and median duration of response were 9.5 months and 12.6 months, respectively. In addition, 64% of responders were still on treatment, and continuing to respond. The median progression free survival was 8.3 months and median overall survival was not reached. Grade 3/4 treatment related adverse events were observed in 26% of patients, with one Grade 5 event.

Virtual Investor Event

Mirati Therapeutics will host a virtual Investor Event on Monday, September 20, 2021 at 8:30 a.m. ET / 5:30 a.m. PT.

Company executives will discuss:

A top-line update from the Phase 2 registrational cohort of the KRYSTAL-1 study evaluating adagrasib in previously-treated patients with KRASG12C-mutated NSCLC
Findings from the colorectal cancer (CRC) cohort of the Phase 1/2 KRYSTAL-1 study evaluating adagrasib as monotherapy and in combination with cetuximab in patients with heavily pretreated CRC harboring the KRASG12C mutation, as presented at the 2021 European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress
Results from the Phase 2 MRTX-500 study evaluating sitravatinib combined with nivolumab in patients with non-squamous NSCLC who progressed on or after prior checkpoint inhibitor therapy, to be presented at the 2021 ESMO (Free ESMO Whitepaper) Congress
Investors and the general public are invited to register and listen to a live webcast of the event through the "Investors and Media" section on Mirati.com. A replay of the event will be available shortly after the conclusion of the event.

About the KRYSTAL-1 Study

KRYSTAL-1 is an open-label Phase 1/2 multiple expansion cohort trial evaluating adagrasib as monotherapy and in combination with other anticancer therapies in patients with advanced solid tumors harboring the KRASG12C mutation.

About KRASG12C in Non-Small Cell Lung Cancer

Lung cancer is one of the most common cancers worldwide, accounting for 2.21 million new cases and 1.8 million deaths worldwide in 2020. Lung cancer consists of non-small cell lung cancer (NSCLC) in approximately 85 percent of cases and small cell lung cancer (SCLC) in approximately 15 percent of cases. KRASG12C is the most common KRAS mutation in NSCLC, present in approximately 14 percent of patients with lung adenocarcinoma, and is a biomarker mutation of poor prognosis.

About Adagrasib (MRTX849)

Adagrasib is an investigational, highly selective, and potent oral small-molecule inhibitor of KRASG12C that is optimized to sustain target inhibition, an attribute that could be important to treat KRASG12C-mutated cancers, as the KRASG12C protein regenerates every 24-48 hours. Adagrasib is a being evaluated as monotherapy and in combination with other anti-cancer therapies in patients with advanced KRASG12C-mutated solid tumors, including non-small cell lung cancer (NSCLC), colorectal cancer and pancreatic cancer. For more information visit Mirati.com/science.

On September 20, 2021 XOMA Corporation (Nasdaq: XOMA) ("XOMA" or the "Company") reported its Board of Directors has authorized the following cash dividends to holders of XOMA’s Series A and Series B Cumulative Preferred Stock (Press release, Xoma, SEP 20, 2021, View Source [SID1234588008]):

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Holders of the 8.625% Series A Cumulative Perpetual Preferred Stock (Nasdaq: XOMAP) shall receive a cash dividend equal to $0.53906 per share.

Holders of depositary shares, each representing 1/1000 of a share of XOMA’s 8.375% Series B Cumulative Perpetual Preferred Stock (Nasdaq: XOMAO), shall receive a cash dividend equal to $0.52344 per depositary share.

The preferred dividends will be paid on or about October 15, 2021, to respective holders of record at the close of business on October 1, 2021.

On September 20, 2021 Verastem Oncology (Nasdaq:VSTM), a biopharmaceutical company committed to advancing new medicines for patients battling cancer, reported a clinical collaboration agreement with Amgen to evaluate the combination of VS-6766, Verastem Oncology’s investigational dual RAF/MEK inhibitor, with Amgen’s KRAS G12C inhibitor LUMAKRASTM (sotorasib) in KRAS G12C-mutant non-small cell lung cancer (NSCLC) (Press release, Verastem, SEP 20, 2021, View Source [SID1234588006]).

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The Phase 1/2 trial will evaluate the safety, tolerability and efficacy of VS-6766 in combination with LUMAKRASTM in patients with KRAS G12C-mutant NSCLC who have not been previously treated with a KRAS G12C inhibitor as well as in patients who have progressed on a KRAS G12C inhibitor. The study will therefore investigate the potential benefits of a more complete vertical blockade of the RAS pathway with the combination of VS-6766 (RAF/MEK blockade) with LUMAKRASTM (G12C inhibition) in KRAS G12C-mutant locally advanced or metastatic NSCLC.

"Recent data indicate that acquired resistance to KRAS G12C inhibitors in patients occurs predominantly through additional mutations in the RAS pathway, many of which may be addressed with a downstream inhibitor such as VS-6766,"1 said Ramaswamy Govindan, M.D., Professor, Department of Medicine, Oncology Division at Washington University School of Medicine and lead investigator of the study. "This clinical study of VS-6766 and LUMAKRASTM will build on preclinical data showing synergy between these two agents, including tumor regression through deeper blockade of ERK pathway signaling."2

"We are pleased to partner with Amgen on this important research that could potentially expand treatment options for patients with KRAS G12C-mutant NSCLC," said Brian Stuglik, CEO of Verastem Oncology. "This collaboration advances our strategy to fully explore the potential of VS-6766 as a backbone of therapy to treat RAS pathway-driven cancers."

Verastem Oncology expects to initiate the clinical trial with VS-6766 and LUMAKRASTM by the end of 2021.

About KRAS Mutant Non-Small Cell Lung Cancer (NSCLC)

Approximately 85% of lung cancers are non-small cell lung cancer (NSCLC), which are the single leading cause of cancer deaths worldwide.3 KRAS mutation occurs in approximately 25% of NSCLC adenocarcinoma patients.4 Two of the most common types of KRAS mutations are G12C, which occurs in approximately 13% of patients with NSCLC adenocarcinoma, as well as G12V, which is present in approximately 7% of NSCLC.5,6 Currently, there is a high unmet need in the second-line treatment of KRAS mutant NSCLC.3,7

About VS-6766

VS-6766 (formerly known as CH5126766 and RO5126766) is a unique inhibitor of the RAF/MEK signaling pathway. In contrast to other MEK inhibitors in development, VS-6766 blocks both MEK kinase activity and the ability of RAF to phosphorylate MEK. This unique mechanism allows VS-6766 to block MEK signaling without the compensatory activation of MEK that appears to limit the efficacy of other inhibitors. The U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation for the combination of Verastem Oncology’s investigational RAF/MEK inhibitor VS-6766, with defactinib, its FAK inhibitor, for the treatment of all patients with recurrent low-grade serous ovarian cancer (LGSOC) regardless of KRAS status after one or more prior lines of therapy, including platinum-based chemotherapy.8

Verastem Oncology has initiated Phase 2 registration-directed trials of VS-6766 with defactinib in patients with recurrent LGSOC and in patients with recurrent KRAS-G12V mutant NSCLC as part of its RAMP (Raf And Mek Program) clinical trials.

On September 20, 2021 Tempest Therapeutics, Inc. (Nasdaq: TPST), a clinical-stage oncology company developing potentially first-in-class therapeutics that combine both targeted and immune-mediated mechanisms, reported the first patient has been dosed in the global randomized Phase 1b/2 clinical study evaluating TPST-1120, Tempest’s small molecule PPAR⍺ antagonist, in combination with the standard-of-care regimen of atezolizumab and bevacizumab in the first-line treatment of patients with advanced or metastatic hepatocellular carcinoma ("HCC") (Press release, Tempest Therapeutics, SEP 20, 2021, View Source [SID1234588005]). The trial is being conducted under a clinical collaboration with F. Hoffman La-Roche ("Roche").

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"The initiation of this randomized TPST-1120 study in collaboration with Roche marks significant progress in the advancement of the Tempest clinical pipeline," said Sam Whiting, MD, Ph.D., chief medical officer of Tempest. "We continue to be excited about TPST-1120’s mechanism of action and are encouraged by its safety profile and early signals of clinical benefit seen in both monotherapy and combination studies. The Tempest team looks forward to further evaluation of TPST-1120 in this randomized combination in the first-line treatment of patients with HCC."

"Atezolizumab plus bevacizumab is the standard-of-care for most patients with HCC, but new combinations are needed to further improve patient outcomes," said Mark Yarchoan, M.D., Assistant Professor of Medicine at Johns Hopkins University School of Medicine and Co-Director of the Liver Cancer Multidisciplinary Clinic. "In preclinical models, TPST-1120’s mechanism of action is complementary with the immune mechanism of atezolizumab and the anti-VEGF mechanism of bevacizumab. Additionally, activation of the B-catenin pathway, which is quite common in HCC, has been associated with direct benefit from targeting the metabolic pathway inhibited by TPST-1120. For these reasons, the triplet regimen of the three drugs together is particularly interesting for evaluation in patients with HCC."

The Phase 1b/2 global randomized study will evaluate TPST-1120 in combination with the standard-of-care regimen of atezolizumab and bevacizumab in patients with advanced or metastatic HCC not previously treated with systemic therapy. At least 40 and up to 60 patients will receive the TPST-1120 combination at approximately 25 sites worldwide including the United States, Asia, and Europe, and will be compared to the standard-of-care atezolizumab and bevacizumab regimen with primary objectives of anti-tumor activity and safety. Under the terms of the collaboration agreement, Roche will manage the study operations for this global, multicenter trial. Tempest retains global development and commercialization rights to TPST-1120.

About TPST-1120

TPST-1120 is an oral, small molecule, selective PPAR⍺ antagonist. Tempest’s preclinical data suggest that TPST-1120 can kill tumor cells directly and target suppressive immune pathways in the tumor microenvironment. Both types of targeted cells can be dependent on fatty acid metabolism, which is regulated by the PPAR⍺ transcription factor. In extensive non-clinical studies, TPST-1120 as a monotherapy or in combination with other anti-cancer drugs resulted in significant reductions in tumor growth and stimulation of durable anti-tumor immunity. In an ongoing Phase 1 clinical trial, TPST-1120 has been well-tolerated by patients with advanced cancers as monotherapy and in combination with the PD-1 inhibitor nivolumab, and has demonstrated tumor reduction (including according to RECIST criteria), as well as biomarker modulation.

About Hepatocellular Carcinoma

HCC is an aggressive cancer with limited treatment options and is a major cause of cancer deaths worldwide. Every year, more than 815,000 people worldwide are diagnosed with HCC. In the US, the number of liver cancer cases have more than tripled since 1980 and HCC represents the fastest-rising cause of cancer-related death, while in Europe, liver cancer is also on the rise. HCC develops predominantly in people with cirrhosis due to chronic hepatitis (B or C) or alcohol consumption, and typically presents at an advanced stage. The prognosis for unresectable HCC remains poor, with few systemic therapeutic options and a 1-year survival rate of less than 50% following diagnosis.

On September 20, 2021 RAPT Therapeutics, Inc. (Nasdaq: RAPT), a clinical-stage, immunology-based biopharmaceutical company focused on discovering, developing and commercializing oral small molecule therapies for patients with significant unmet needs in oncology and inflammatory diseases, reported that Brian Wong, M.D., Ph.D., President and CEO, will present at the 2021 Cantor Virtual Healthcare Conference on Monday, September 27, 2021 at 2:00 p.m. EST (Press release, RAPT Therapeutics, SEP 20, 2021, https://investors.rapt.com/news-releases/news-release-details/rapt-therapeutics-present-2021-cantor-virtual-healthcare [SID1234588003]).

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To access the live webcast or subsequent archived recording of the company presentation, please visit the RAPT Therapeutics website at https://investors.rapt.com/events-and-presentations.