On December 22, 2020 Amgen (NASDAQ: AMGN) reported submission of a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for sotorasib, an investigational KRASG12C inhibitor, for the treatment of adult patients with previously treated KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC) (Press release, Amgen, DEC 22, 2020, View Source [SID1234573242]).

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"Just over two years since the first patient was dosed, sotorasib is now on track to potentially be the first approved targeted therapy for patients with previously treated NSCLC harboring the KRAS G12C mutation," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "With this submission to EMA, Amgen is continuing to rapidly advance the KRASG12C inhibitor clinical program to bring this innovative potential therapy to patients globally as quickly as possible."

KRAS G12C is the most common KRAS mutation in NSCLC.1 Approximately 13% of patients with NSCLC harbor the KRAS G12C mutation and each year approximately 33,000 new patients in the EU-27 are diagnosed with KRAS G12C-mutated NSCLC.1,2 There is a high unmet need and poor outcomes in the second-line treatment of KRAS G12C-driven NSCLC and, currently, there are no KRAS G12C targeted therapies approved. 3,4,5

The submission is supported by positive Phase 2 results in patients with locally advanced or metastatic NSCLC with KRAS G12C mutation from the CodeBreaK 100 clinical study, whose cancer had progressed despite prior treatment with chemotherapy and/or immunotherapy. In the Phase 1 study, treatment with sotorasib provided durable anticancer activity with a positive benefit-risk profile.6 These results will be presented at the International Association for the Study of Lung Cancer (IASLC) 2020 World Conference on Lung Cancer (WCLC) Presidential Symposium in January 2021.

About Sotorasib
Amgen has taken on one of the toughest challenges of the last 40 years in cancer research by developing sotorasib, an investigational KRASG12C inhibitor.7 Sotorasib was the first KRASG12C inhibitor to enter the clinic and is being studied in the broadest clinical program exploring 10 combinations with global sites spanning four continents. In just over two years, the sotorasib clinical program CodeBreaK has established the deepest clinical data set with more than 600 patients studied across 13 tumor types.

Sotorasib has demonstrated a positive benefit-risk profile with fast, deep and durable anticancer activity in patients with advanced non-small cell lung cancer (NSCLC) harboring the KRAS G12C mutation with a once daily oral formulation. Promising responses have also been observed in multiple other solid tumors.7

About CodeBreaK
The CodeBreaK clinical development program for Amgen’s investigational drug sotorasib is designed to treat patients with an advanced solid tumor with the KRAS G12C mutation and address the longstanding unmet medical need for these cancers. As the most advanced KRAS G12C clinical development program, CodeBreaK has enrolled more than 600 patients across 13 tumor types since its inception.

CodeBreaK 100, the Phase 1 and 2, first-in-human, open-label multicenter study, enrolled patients with KRAS G12C-mutated solid tumors. Eligible patients must have received a prior line of systemic anticancer therapy, consistent with their tumor type and stage of disease. The primary endpoint for the Phase 2 study was centrally assessed objective response rate. The Phase 2 trial in NSCLC enrolled 126 patients, 123 of whom had centrally evaluable lesions by RECIST at baseline. The Phase 2 trial in colorectal cancer (CRC) is fully enrolled and topline results are expected in 2021.

A global Phase 3 randomized active-controlled study comparing sotorasib to docetaxel in patients with KRAS G12C-mutated NSCLC (CodeBreaK 200) is currently recruiting. Amgen also has several Phase 1b combination studies across various advanced solid tumors (CodeBreaK 101) open for enrollment.

For information, please visit www.codebreaktrials.com.

About Amgen Oncology
Amgen Oncology is searching for and finding answers to incredibly complex questions that will advance care and improve lives for cancer patients and their families. Our research drives us to understand the disease in the context of the patient’s life – not just their cancer journey – so they can take control of their lives.

For the last four decades, we have been dedicated to discovering the firsts that matter in oncology and to finding ways to reduce the burden of cancer. Building on our heritage, Amgen continues to advance the largest pipeline in the Company’s history, moving with great speed to advance those innovations for the patients who need them.

At Amgen, we are driven by our commitment to transform the lives of cancer patients and keep them at the center of everything we do.

To learn more about Amgen’s innovative pipeline with diverse modalities and genetically validated targets, please visit AmgenOncology.com. For more information, follow us on www.twitter.com/amgenoncology.

On December 22, 2020 Sosei Group Corporation, a world leader in GPCR-focused structure-based drug design and development, and Captor Therapeutics, a European leader in targeted protein degradation, have entered a strategic technology collaboration focused on the discovery and development of novel small molecules that target the degradation of disease-associated G protein-coupled receptors (GPCRs) (Press release, Captor Therapeutics, DEC 22, 2020, View Source [SID1234623171]).

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Targeted protein degradation (TPD) is an approach whereby the body’s natural process for degrading proteins is diverted using small molecule drugs to eliminate disease-causing proteins. The selective destruction of such proteins is expected to have multiple advantages over classical drugs such as inhibitors and antibodies for the development of novel therapeutics against a broad range of diseases.

Sosei Heptares and Captor initially will focus on identifying small molecules targeting a GPCR with a key role in a strongly validated signalling pathway implicated in gastrointestinal disorders. A further aim of the collaboration is to generate high resolution structural information around the GPCR-E3 ligase complex to enhance drug discovery efforts as well as provide proof of concept for targeted degradation discovery approaches with other GPCRs and other target classes.

The collaboration combines Sosei Heptares’ structure-based drug design (SBDD) platform, including its structural insights around the target, and its deep understanding of GPCR pharmacology, together with Captor’s proprietary TPD Optigrade, platform and extensive know-how and expertise in protein degradation.

Since 2017, Captor has raised approximately €40 million from private investors and non-dilutive funding sources, allowing it to create an advanced TPD platform and establish five pipeline programs in cancer and autoimmune diseases.

Captor’s Optigrade platform is focused on improving the selectivity and performance of first-generation degrader drugs. The principle of TPD is to use small molecules to commit the target protein into the E3 ligase-mediated degradation pathway thereby eliminating or reducing its activity. Molecular glues and bifunctional degraders are two different approaches to promote the direct binding of a specific E3 ligase to the target protein, and in each case, Captor has developed molecules with improved selectivity. These approaches can also be coupled with Captor’s novel E3 Ligase ligands (Lilis) which take advantage of Captor’s extensive library of E3 Ligase enzymes to create a new generation of degrader drugs.

Promising leads will be progressed using the partners’ complementary discovery skills, resources and development capabilities for subsequent development and commercialization.

Under the agreement, the companies will jointly conduct the discovery and development program and will co-own any resulting products, with Sosei Heptares supporting initial R&D costs. No further financial details are disclosed.

Miles Congreve, Chief Scientific Officer of Sosei Heptares, commented: "Targeted protein degradation is a promising approach to drug discovery that is gaining strong interest in the pharmaceutical industry. However, there has so far been limited progress in applying this exciting approach to membrane-associated proteins such as GPCRs. We can see a real opportunity to expand the reach of our SBDD and GPCR pharmacology expertise into this area; GPCRs themselves play key roles in disease yet are often difficult to drug. We are delighted to enter this collaboration with Captor, which has developed multiple novel approaches to identify small molecules that promote TPD. We are excited to explore the potential of this unique combination of technologies to develop a novel GPCR degraders platform, opening up so far intractable drug targets for us to address."

Michal J. Walczak, Chief Scientific Officer of Captor Therapeutics, added: "This is an important partnership for both Captor and Sosei Heptares. We believe that the successful application of targeted protein degradation to G Protein-Coupled Receptors will open new avenues in medicine and will maximize treatment opportunities for patients. Working with Sosei Heptares, a global leader in targeting GPCRs, is an exciting opportunity to create truly novel medicines and unlock TPD for GPCR targets, which will constitute another cornerstone validating the potential of TPD as an emerging drug discovery technology."

On December 22, 2020 Advaxis, Inc. (Nasdaq: ADXS), a clinical-stage biotechnology company focused on the development and commercialization of immunotherapy products, reported that it received a positive determination from the Nasdaq Stock Market granting approval of the Company’s request to transfer its listing to the Nasdaq Capital Market from the Nasdaq Global Select Market (Press release, Advaxis, DEC 22, 2020, View Source [SID1234573207]). The Company’s securities will begin trading on the Nasdaq Capital Market effective at the start of trading on December 24, 2020. The Company’s shares will continue to trade on Nasdaq under the symbol "ADXS."

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The Company’s stock price has traded below the minimum bid price necessary to maintain its listing on the Nasdaq Global Select Market (and now, the Nasdaq Capital Market). On December 22, 2020, Advaxis received notification from Nasdaq that the Company has been granted an additional 180-day compliance period, or until June 21, 2021, to regain compliance with the minimum $1.00 bid price per share requirement of Nasdaq’s Marketplace Rule 5550(a)(2) (the "Rule"). Nasdaq’s determination to grant the additional 180-day compliance period was based on the Company meeting the continued listing requirements of the Nasdaq Capital Market with the exception of the bid price requirement, and the Company having provided written notice of its intention to cure the deficiency during the additional compliance period, including effecting a reverse stock split if necessary.

According to Nasdaq, if at any time before June 21, 2021 the bid price of the Company’s common stock closes at $1.00 per share or more for a minimum of 10 consecutive business days, the Company will regain compliance with the Rule and the matter will be closed.

If the Company does not meet the minimum bid requirement during the additional 180-day grace period, Nasdaq will provide written notification to the Company that its common stock will be subject to delisting. At such time, the Company may appeal the delisting determination to a Nasdaq Hearings Panel ("Panel"). The Company would remain listed pending the Panel’s decision. There can be no assurance that, if the Company does appeal a subsequent delisting determination by the Staff to the Panel, that such appeal would be successful.

On December 22, 2020 Neomorph reported a $109 million Series A financing to advance a proprietary targeted protein degradation platform and specific programs (Press release, Neomorph, DEC 22, 2020, View Source [SID1234627533]). Deerfield Management Company established Neomorph earlier this year with scientific founders Phil Chamberlain, DPhil; Eric Fischer, PhD; Benjamin Ebert, MD, PhD; and Scott Armstrong, MD, PhD.

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The founding management team comprises pharmaceutical veterans with deep industry knowledge in targeted protein degradation drug discovery. Led by Dr. Chamberlain as President and Chief Scientific Officer, Neomorph has recruited top industry talent who have made major contributions to the field, including: Rohan Beckwith, PhD; Gang Lu, PhD; Mary Matyskiela, PhD; Ben Wen, PhD; and Samer Chmait.

Targeted protein degradation offers opportunities to develop novel therapeutics across a broad range of disease areas, including oncology. Strategies for protein degradation have been shown to solve critical problems in drug discovery by enabling researchers to target previously "undruggable" proteins that lack suitable binding pockets required for conventional drug activity.

Of particular note, Neomorph’s founders are responsible for several fundamental scientific developments in the "molecular glue" field. Molecular glues are types of molecules that encourage proteins to come together that normally would not interact. Neomorph plans to build on the collective pivotal research findings of the team to advance the technology of targeted protein degradation and solve critical problems in human health.

"Having the ability to achieve this milestone during these unprecedented times is a testament to Neomorph’s capabilities in the protein degradation and molecular glue space," said Dr. Fischer, who is also an Associate Professor in the Department of Biological Chemistry and Molecular Pharmacology at Harvard Medical School and an Independent Investigator at the Dana-Farber Cancer Institute. "I am humbled to be a part of a team poised to make real strides in advancing the science. We believe we are in an excellent position to take our technology to the next level with the ultimate goal of delivering transformative treatments to patients in need."

"The Neomorph team has deep expertise in pharmacological approaches to targeted protein degradation and we are excited to be developing new therapeutics for patients with diseases that are currently difficult to treat," said Dr. Armstrong, who is also David G. Nathan, MD, Professor of Pediatrics at Harvard Medical School and the Dana-Farber Cancer Institute.

Utilizing Deerfield seed funding and operational support since the first quarter of 2020, Neomorph has established a research site in San Diego at the Genesis Science Center in Sorrento Mesa, California. This Series A financing will position Neomorph to further develop its platform, advance lead programs, and expand the research team.

"As a drug strategy, protein degradation has enormous potential as it leverages the cell’s natural system for clearing unwanted or damaged proteins," said Deerfield Partner Cameron Wheeler, PhD. "We believe there continues to be a significant opportunity in protein degradation, in particular as it relates to the glue space. Neomorph is in an exceptional position and couldn’t have a more seasoned and knowledgeable team in place to interrogate and advance drug targets. The Company’s success could potentially lead to life-altering therapies."

Neomorph will benefit from a close collaboration with the Center for Protein Degradation at Dana Farber Cancer Institute. With its investment, this expands Deerfield’s commitment in the space given the firm’s longstanding partnership and collaboration with Dana Farber Cancer Institute.

On December 22, 2020 Spectrum Pharmaceuticals, Inc. (NasdaqGS: SPPI), a biopharmaceutical company focused on novel and targeted oncology therapies, reported that the U.S. Food and Drug Administration (FDA) has agreed to the submission of an NDA based on data from Cohort 2 of its Phase 2 clinical trial, ZENITH20, which evaluated previously treated patients with non-small cell lung cancer (NSCLC) with HER2 exon 20 insertion mutations (Press release, Spectrum Pharmaceuticals, DEC 22, 2020, View Source [SID1234573208]). The company also reported that its pre-specified primary endpoint in its Phase 2 clinical trial evaluating poziotinib in first-line NSCLC patients with EGFR exon 20 insertion mutations was not met in Cohort 3. Spectrum additionally reported that preliminary data from patients receiving 8 mg of poziotinib twice daily demonstrated meaningful improvement in tolerability as measured by adverse events and dosing interruptions.

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"The agreement with the FDA to proceed with the submission of a new drug application is a significant milestone for the poziotinib program," said Joe Turgeon, President and CEO of Spectrum Pharmaceuticals. "The improved tolerability from the BID dosing could have a meaningful impact on the overall safety and efficacy profile of poziotinib in an area of high unmet medical need."

The company had a successful pre-NDA meeting with the FDA which resulted in an agreement to submit an NDA for poziotinib. During the meeting, Spectrum confirmed with the FDA that Cohort 2 data could serve as the basis of an NDA submission. The company will continue to work with the FDA as it prepares the application for submission in 2021. Cohort 2 enrolled 90 patients who received an oral once daily dose of 16 mg of poziotinib. The intent-to-treat analysis demonstrated a confirmed objective response rate (ORR) of 27.8% (95% Confidence Interval (CI), 18.9%-38.2%). The observed lower bound of 18.9% exceeded the pre-specified lower bound of 17%. The median duration of response was 5.1 months and the median progression free survival was 5.5 months. In this cohort, 87% of patients had drug interruptions with 11 patients (12%) permanently discontinuing due to adverse events. 13 patients (14%) had treatment-related serious adverse events.

"We are pleased that the FDA meeting confirmed that Cohort 2 data can serve as the basis of a NDA submission and our team is diligently working on preparing our file for submission in 2021," said Francois Lebel, M.D., Chief Medical Officer of Spectrum Pharmaceuticals. "While Cohort 3 did not meet its pre-specified ORR endpoint, we are seeing evidence of clinical activity with a disease control rate (DCR) of 86% and progression free survival data of 7.2 months." Dr. Lebel added, "The preliminary data from Cohort 5 with 8 mg twice daily dosing is supporting our hypothesis that this new dosing paradigm improves tolerability substantially, with Grade 3 adverse events reduced by about a third. We believe that improved tolerability and reduced drug dosing interruptions are key to patients staying on the drug longer and could potentially enhance anti-tumor effectiveness across the various EGFR and HER2 cohorts. These early findings, if confirmed, could benefit the entire poziotinib program."

Cohort 3 of the ZENITH20 clinical trial enrolled a total of 79 patients who received an oral once daily dose of 16 mg of poziotinib. The median time of follow up of all patients was 9.2 months with 12 ongoing patients still on treatment. The intent-to-treat analysis showed that 22 patients had a partial response (by RECIST) and 68 patients had stable disease for an 86.1% DCR. 91% of patients experienced tumor reduction with a median reduction of 25.5%. The confirmed ORR was 27.8% (95% CI 18.4-39.1%). Based on the pre-specified statistical hypothesis for the primary endpoint, the observed lower bound of 18.4% did not meet the pre-specified lower bound of >20%. The median duration of response was 6.5 months and the median progression free survival was 7.2 months. The safety profile was similar with the type of adverse events observed with other second-generation EGFR tyrosine kinase inhibitors. Grade 3 treatment related rash was 33% and diarrhea was 23%. 94% of patients had drug interruptions with 6 patients (8%) permanently discontinuing due to adverse events.

Preliminary data from Cohort 5 for patients with exon 20 insertion mutations receiving 8 mg twice daily dosing shows improved tolerability versus patients who received the 16 mg once daily dose. The data from this cohort includes patients with both EGFR and HER2 mutations. In Cycle 1, the incidence of Grade 3 or higher treatment related adverse events (rash, diarrhea and stomatitis) decreased by 32% for patients receiving the 8 mg twice daily dose. In addition, dose interruptions were reduced by 38% for the 8 mg twice daily dose versus the 16 mg once daily dose. No new types of adverse events were observed with the twice daily dosing regimen.

Conference Call and Webcast

The company’s management will host a webcast and conference call today, December 22, 2020, at 4:30 p.m. ET / 1:30 p.m. PT. The live call may be accessed by dialing (877) 837-3910 for domestic callers and (973) 796-5077 for international callers and entering the conference ID#: 5036836. A live webcast of the call will be available from the Investor Relations section of the company’s website at View Source and will be archived there shortly after the live event.

About Poziotinib

Poziotinib is a novel, oral epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) that inhibits the tyrosine kinase activity of EGFR as well as HER2 and HER4. Importantly this, in turn, leads to the inhibition of the proliferation of tumor cells that overexpress these receptors. Mutations or overexpression/amplification of EGFR family receptors have been associated with a number of different cancers, including non-small cell lung cancer (NSCLC), breast cancer, and gastric cancer. The company holds an exclusive license from Hanmi Pharmaceuticals to develop, manufacture, and commercialize poziotinib worldwide, excluding Korea and China. Poziotinib is currently being investigated by the company and Hanmi in several mid-stage trials in multiple solid tumor indications.

About ZENITH20

The ZENITH20 trial is comprised of 7 independent cohorts. Cohorts 1 – 4 are each independently powered for a pre-specified statistical hypothesis with a primary endpoint of ORR. Cohorts 5 – 7 are exploratory. In December 2019, the company reported that the primary endpoint for Cohort 1 (EGFR) was not met but clinical activity was seen. Based on the results of Cohort 1, the company has amended the protocol for ZENITH20 to explore additional twice-daily dosing regimens as well as lower single daily dosage. In September 2020, the company reported that Cohort 2 met its primary endpoint. Cohorts 4 – 7 are still enrolling patients.