On March 18, 2021 Foghorn Therapeutics Inc. (Nasdaq: FHTX), a company pioneering the discovery and development of a new class of medicines targeting genetically determined dependencies within the chromatin regulatory system, reported a corporate update in conjunction with its 10-K filing for the year ended December 31, 2020 (Press release, Foghorn Therapeutics, MAR 18, 2021, View Source [SID1234576869]).

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"With IND clearance for FHD-286 in both relapsed and/or refractory AML and metastatic uveal melanoma, we are currently initiating our first two clinical studies with initial data possible by the end of 2021, a significant milestone for our company," said Adrian Gottschalk, Chief Executive Officer of Foghorn Therapeutics. "At the same time, the IND for our second program, FHD-609, a protein degrader targeting BRD9 for the treatment of synovial sarcoma, is on track for submission in the second quarter. We have a broad pipeline of programs that continue to advance, including both an inhibitor and protein degrader targeting BRM and a protein degrader program targeting ARID1B. These programs represent two of the most prevalent synthetic lethal relationships in cancer."

Using its proprietary Gene Traffic Control platform, Foghorn is advancing a novel class of therapeutics, including targeting multiple transcription factors, exploiting synthetic lethal relationships in the chromatin regulatory system, while in parallel bolstering its protein degradation capabilities. The company is well resourced to achieve several clinical and preclinical milestones over the coming quarters.

Recent Corporate Highlights:

Completed successful initial public offering (IPO): In October, Foghorn completed a successful initial public offering of common stock that raised gross proceeds, before underwriting discounts and commissions, of approximately $135.2 million.
Received IND clearances for FHD-286: Received IND clearance for its first therapeutic candidate, FHD-286, in metastatic uveal melanoma and relapsed/refractory AML in late December and early January, respectively. FHD-286 is a highly potent, selective, allosteric, small molecule inhibitor of BRG1/BRM.
Key Upcoming Milestones

FHD-286 first patient to be dosed: Expect to dose the first patient in the company’s phase I clinical studies, being conducted in metastatic uveal melanoma and relapsed/refractory AML, in the near future. Foghorn expects to report initial data by as early as year-end 2021.
FHD-609 IND submission: FHD-609, a highly potent, selective, intravenous, small molecule protein degrader of BRD9, is initially being developed for the treatment of synovial sarcoma with the intention to expand into additional indications, including SMARCB1-deleted tumors. The company is on track to submit an IND with the FDA in the second quarter of 2021.
Upcoming Events

AACR Conference: Foghorn is scheduled to present a poster and chair a panel at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Meeting 2021, which is being held virtually from April 10-15. The poster presentation, entitled, "Discovery of BAF Inhibitors for the Treatment of Transcription Factor-Driven Cancers," will be available on-demand beginning 8:30AM on Saturday, April 10. In addition, Steve Bellon, Foghorn Therapeutics’ Senior Vice President of Drug Discovery, will chair a panel with an accompanying presentation, "Targeting the BAF Complex in Cancer," on Wednesday, April 14 from 2:30-3:30PM ET.
Financial Condition

Foghorn reported cash, cash equivalents and marketable securities of $185.8 million as of December 31, 2020 compared with $15.0 million as of December 31, 2019.

On March 18, 2021 Pyxis Oncology ("Pyxis" or the "Company") reported that it has entered into a worldwide license agreement with Pfizer Inc. (NYSE:PFE) for the development and commercialization of two antibody-drug conjugate (ADC) candidates and a license to Pfizer’s ADC technology platform, enabling expansion of its ADC portfolio and further strengthening its developmental capabilities (Press release, Pyxis Oncology, MAR 18, 2021, View Source [SID1234576868]).

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"This collaboration represents successful execution of our overarching corporate strategy to marry in-house organic growth with strategic in-licensing and partnerships to develop our multi-asset multi-platform portfolio," said Lara Sullivan, M.D., Chief Executive Officer of Pyxis. "We look forward to advancing these candidates to the clinic and ultimately achieving the company’s vision to bring new treatment options to patients with difficult-to-treat cancer."

Under the terms of the licensing agreement, Pfizer will provide Pyxis with a worldwide, royalty-bearing license to develop and commercialize two innovative ADC candidates, PYX-201 and PYX-203. Pfizer will receive an upfront payment and equity in Pyxis and is eligible to receive development and sales-based milestone payments and tiered royalties on potential sales. As part of this agreement, Pyxis also was granted a license to Pfizer’s ADC platform, including various payload classes, linker technology and site-specific conjugation techniques for the future development of additional ADCs. Pfizer will also continue to support the development and advancement of this portfolio through an equity investment made by Pfizer Ventures.

Ronald Herbst, Ph.D., Chief Scientific Officer of Pyxis, said, "The early generations of ADCs demonstrated significant potency, but considerable room remains for innovation to generate highly effective ADCs with an improved safety profile. PYX-201 and PYX-203 represent the next generation of ADCs that use innovative conjugation technologies. By combining highly specific antibodies targeting clinically validated tumor markers with established linkers and both novel and proven payloads, we are excited to translate the extensive validating preclinical studies conducted by Pfizer to an improved clinical profile for patients."

Jeff Settleman, Ph.D., Pfizer’s Chief Scientific Officer of oncology research & development, added, "The Pyxis team of industry veterans led by Dr. Sullivan and Dr. Herbst has the experience needed to maximize the clinical potential of these therapeutics. This agreement underscores our commitment to ensure these molecules reach patients as quickly as possible. We look forward to the team’s advancement of these therapeutics based on the promise of ADC technology to significantly impact the treatment landscape."

PYX-201 is a first-in-class non-internalizing ADC that targets a tumor-restricted antigen that is overexpressed in several solid tumor types to selectively kill tumor cells while enhancing a robust anti-cancer immune response. PYX-203 is an ADC that targets an antigen expressed in certain hematologic malignancies. PYX-203 utilizes a highly potent DNA-damaging agent designed to reduce the potential development of drug resistance and disease relapse.

On March 18, 2021 Exelixis, Inc. (Nasdaq:EXEL) reported a clinical trial collaboration and supply agreement with Merck KGaA, Darmstadt, Germany and Pfizer for the ongoing phase 1b dose escalation study STELLAR-001 (previously called "XL092-001"), adding three new cohorts that will evaluate the safety and tolerability of XL092, Exelixis’ novel next generation tyrosine kinase inhibitor (TKI), in combination with avelumab (BAVENCIO), an anti-PD-L1 immune checkpoint inhibitor (ICI), in patients with locally advanced or metastatic urothelial carcinoma (UC) (Press release, Exelixis, MAR 18, 2021, View Source [SID1234576867]). Avelumab is being co-developed and co-commercialized by Merck KGaA, Darmstadt, Germany and Pfizer. Exelixis is sponsoring the STELLAR-001 clinical trial, and Merck KGaA, Darmstadt, Germany and Pfizer will provide avelumab for use in the trial.

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"We are pleased to collaborate with Merck KGaA, Darmstadt, Germany and Pfizer to study the potential of XL092 in combination with avelumab as part of the broad development program evaluating our novel next generation tyrosine kinase inhibitor across a wide variety of cancers," said Gisela Schwab, M.D., President, Product Development and Medical Affairs and Chief Medical Officer, Exelixis. "Although several therapies are now available to treat bladder cancers, the prognosis for patients with advanced disease remains poor and more options are needed. Evaluating how XL092 may positively impact care when paired with immunotherapy is central to our goal of improving therapeutic outcomes for patients with this and other difficult-to-treat cancers."

Based on the dose-escalation results, the trial has the potential to enroll up to three expansion cohorts evaluating XL092 in combination with avelumab in metastatic UC, including as maintenance therapy, in patients who have progressed following treatment with an ICI, and in patients previously treated with platinum-containing chemotherapy.

XL092 is an investigational, next-generation oral TKI that targets VEGF receptors, MET, AXL, MER and other kinases implicated in the growth and spread of cancer. Preclinical findings presented at the 32nd EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium in October 2020 showed that XL092 in combination with an ICI was more efficacious than either XL092 or anti-PD1 alone. Single-agent avelumab is the only ICI approved in the U.S. for maintenance treatment of patients with locally advanced or metastatic UC that has not progressed with first-line platinum-based chemotherapy.

More information about this trial is available at ClinicalTrials.gov.

About the STELLAR-001 Clinical Trial

Initiated in February 2019, the dose-escalation evaluation of XL092 in the monotherapy arm of the phase 1 trial is ongoing. Once the recommended doses of both single-agent XL092 and XL092 in combination with ICIs are established, the trial will begin to enroll expansion cohorts for patients with UC, castration-resistant prostate cancer (CRPC), clear cell and non-clear cell renal cell carcinoma (RCC), and hormone receptor-positive breast cancer.

About XL092

XL092 is a next-generation oral TKI that targets VEGF receptors, MET, AXL, MER and other kinases implicated in cancer’s growth and spread. In designing XL092, Exelixis sought to build upon the experience and target profile of cabozantinib, the company’s flagship medicine, while improving key characteristics, including clinical half-life. XL092 is the first internally discovered Exelixis compound to enter the clinic following the company’s reinitiation of drug discovery activities.

About Genitourinary Cancers

Genitourinary cancers are those that affect the urinary tract, bladder, kidneys, ureter, prostate, testicles, penis or adrenal glands — parts of the body involved in reproduction and excretion — and include RCC, CRPC and UC.1

Urothelial cancers encompass carcinomas of the bladder, ureter and renal pelvis at a ratio of 50:3:1, respectively.2 Bladder cancer occurs mainly in older people, with 90 percent of patients aged 55 or older.3 With an estimated 84,000 new cases to be diagnosed in 2021, bladder cancer accounts for about five percent of all new cases of cancer in the U.S. each year.3,4 It is the fourth most common cancer in men.5

On March 18, 2021 Debiopharm (www.debiopharm.com), a Swiss-based global biopharmaceutical company, reported the signature of an exclusive license agreement with Merck KGaA, Darmstadt, Germany , a leading science and technology company, for the development and commercialization of xevinapant (Debio 1143) (Press release, Debiopharm, MAR 18, 2021, View Source [SID1234576866]). Xevinapant, a potent, oral of Inhibitor of Apoptosis Proteins (IAP) antagonist, is the only medicine in its class in late-stage clinical development and has the potential to be first in class. Xevinapant is currently being investigated in the pivotal Phase III TrilynX study for previously untreated high-risk locally advanced squamous cell carcinoma of the head and neck (LA SCCHN), in combination with platinum-based chemotherapy and standard fractionation intensity-modulated radiotherapy. Given their strong commercial footprint in the field of head and neck cancer, Merck KGaA, Darmstadt, Germany is the partner of choice to leverage our outstanding phase II data and make xevinapant a transformative therapy for cancer patients.

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Under the terms of the license agreement, Merck KGaA, Darmstadt, Germany receives exclusive rights to develop and commercialize xevinapant worldwide, including in the U.S. Merck KGaA, Darmstadt, Germany will also co-fund with Debiopharm the ongoing Phase III registrational TrilynX study, a global double-blind, placebo-controlled, 700-patient randomized clinical trial to evaluate the efficacy and safety of xevinapant vs. placebo when added to definitive chemoradiotherapy (CRT) in cisplatin-eligible patients with high-risk LA SCCHN.

This global license agreement is a significant achievement that rewards the clinical development efforts conducted by Debiopharm while demonstrating the agility and relevance of the company’s specific and unique business model. By focusing on drug development, Debiopharm can bridge the most innovative discoveries with the best commercial pharmaceutical partners.

"At Debiopharm we are driven by the ambition to cure. Our business model is led by the needs of patients and unmet medical needs. The data for xevinapant to date demonstrate an extremely important potential to improve the standard treatment for patients with head and neck cancer, an indication for which no new treatment has been registered for several decades, Merck KGaA, Darmstadt, Germany’s in-depth knowledge of head and neck cancer and their worldwide commercial capabilities, make them an exceptionally qualified partner to move xevinapant forward, and position it as the next gold standard of care in head and neck cancer and potentially in other indications."
– Bertrand Ducrey, Chief Executive Officer of Debiopharm.

"By bringing our expertise and heritage in head and neck cancer to the development of xevinapant, we have the opportunity to explore an important new treatment option in an area of high unmet need where other approaches, including immunotherapy, have seen limited success, The promising long-term efficacy of xevinapant in the Phase II clinical study suggests that antagonism of IAP has the potential to be a transformative approach in this cancer. We will build on this strong proof of concept, shown in Debiopharm’s robust clinical program for xevinapant, as we continue to develop this potential new standard of care."
– Peter Guenter, Member of the Executive Board of Merck KGaA, Darmstadt, Germany and CEO Healthcare

"Locally advanced head and neck cancer is uniquely debilitating, often impairing the ability to swallow, speak and breathe. With the current standard treatments, at least half of patients will relapse, typically within the first two years. Based on the efficacy seen in the Phase II study, in which adding xevinapant to CRT cut the risk of death by half, this investigational medicine has the potential to offer a much-needed new standard of care."
– Prof. Jean Bourhis, Department Head of Radio-Oncology at the University Hospital of Lausanne and lead investigator of the Phase III TrilynX study.

Previously reported results from the randomized, double-blind Phase II clinical study showed the addition of xevinapant to standard-of-care CRT provided a statistically significant 21% point improvement in locoregional control rate at 18 months, the primary endpoint, vs. placebo and CRT in patients with high-risk LA SCCHN (54% [95% CI: 39 to 69] vs. 33% [95% CI: 20 to 48]; odds ratio 2·69 [95% CI: 1·13 to 6·42]; p=0·026). A significant progression-free survival (PFS) benefit was also observed vs. the control arm after a two-year follow-up period (HR=0.37, 95% CI: 0.18 to 0.76; p=0.0069). At three years of follow-up, xevinapant plus CRT showed a statistically significant 51% reduction in the risk of death versus placebo plus CRT (HR=0.49, 95% CI: 0.26 to 0.92; p=0.0261). About two-thirds of patients in the xevinapant arm were alive at three years, compared with 51% in the control arm.

In February 2020, the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation to xevinapant for treatment of patients with confirmed diagnosis of previously untreated LA SCCHN in combination with current standard of care, platinum-based chemotherapy and standard-fractionation intensity-modulated radiotherapy, based on the Phase II results.

About Head and Neck Cancer
Worldwide, head and neck cancer accounts for more than 650,000 cases and 330,000 deaths annually, making it the 6th most common cancer type. LA SCCHN is a highly debilitating disease that can lead to impaired breathing, swallowing, and speech as it progresses. Despite standard of care CRT, at least 40% to 60% of patients with LA SCCHN develop locoregional or distant relapses, which are usually detected within the first two years of treatment, underscoring the need to identify new therapeutic approaches.

About xevinapant
Xevinapant (Debio 1143) is a potential first-in-class potent oral antagonist of IAPs (Inhibitor of Apoptosis Proteins). In preclinical studies, xevinapant restores sensitivity to apoptosis in cancer cells, thereby depriving them of one of their major resistance mechanisms. As the most clinically advanced IAP antagonist, xevinapant has established proof of efficacy in combination with chemoradiotherapy (CRT) in patients with high-risk locally advanced squamous cell carcinoma of the head and neck (LA SCCHN), with a clinically significant and sustained clinical benefit compared with CRT alone.

Debiopharm’s commitment to patients
Debiopharm develops innovative therapies that target high unmet medical needs in oncology and infectious diseases. Bridging the gap between disruptive discovery products and real-world patient reach, we identify high-potential compounds and technologies for in-licensing, clinically demonstrate their safety and efficacy and then select large pharmaceutical commercialization partners to maximize patient access globally. Debiopharm is known for the development of oxaliplatin, worldwide gold standard treatment in colorectal cancer and of triptorelin, a standard of care for the treatment of prostate cancer. Xevinapant is well positioned to become the third transformative therapy arising from Debiopharm in oncology.

On March 18, 2021 ChromaDex Corp. (NASDAQ:CDXC) reported that its Chief Executive Officer, Rob Fried, and Chief Financial Officer, Kevin Farr, will be presenting virtually at the Zooming with LD investor conference (Press release, ChromaDex, MAR 18, 2021, View Source [SID1234576865]).

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The ChromaDex management team is scheduled to present on Thursday, March 25, 2021 at 12:30 p.m. Eastern Time (9:30 a.m. Pacific Time).

The presentation will be webcast live via the link below on the investor relations section of the Company’s website at www.chromadex.com. ChromaDex management will also attend virtual one-on-one meetings with institutional investors throughout the day. For those interested in having a meeting with ChromaDex please visit www.ldmicro.com for more information.