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.

On March 18, 2021 ARCA biopharma, Inc. (Nasdaq: ABIO), a biopharmaceutical company applying a precision medicine approach to developing genetically targeted therapies for cardiovascular diseases, reported 2020 financial results and provided a corporate update (Press release, Arca biopharma, MAR 18, 2021, View Source [SID1234576863]).

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Dr. Michael Bristow, ARCA’s President and Chief Executive Officer, commented, "We are currently actively enrolling patients in a Phase 2b clinical trial evaluating rNAPc2 as a potential treatment for patients hospitalized with COVID-19 who are at high risk for thrombotic complications, as indicated by elevated D-dimer levels, which are elevated in nearly 70% of hospitalized COVID-19 patients and are associated with adverse clinical outcomes. We believe rNAPc2’s combination of anticoagulant, anti-inflammatory and antiviral properties, give it the potential to be effective in addressing the impact of COVID-19 from multiple pathways. We look forward to sharing the trial results in the third quarter of this year. As a therapeutic aimed at a host response to a disease syndrome, we believe rNAPc2 has therapeutic potential for future viral outbreaks beyond the current pandemic, even after safe and effective vaccines for SARS-CoV-2 are successfully deployed."

Pipeline Update

rNAPc2 (AB201) – a small recombinant protein being developed as a potential treatment for RNA virus associated disease, initially focusing on COVID-19.

Phase 2b clinical trial evaluating rNAPc2 as a potential treatment for patients hospitalized with COVID-19 initiated in December 2020.
Phase 2b topline data anticipated in the third quarter of 2021.
U.S. Food and Drug Administration (FDA) designated the investigation of rNAPc2 as a potential treatment for COVID-19 as a Fast Track development program.
GencaroTM (bucindolol hydrochloride) – a pharmacologically unique beta-blocker and mild vasodilator being developed as a potential genetically-targeted treatment for atrial fibrillation (AF) in patients with heart failure (HF).

In February 2021, ARCA was issued a new patent by the United States Patent and Trademark Office (USPTO) for use of Gencaro in treating AF in the HF population that ARCA plans to enroll in Phase 3 development, a population that includes more than half of all HF patients in the United States and Europe and has few approved or effective drug therapies. The Company believes this patent would provide effective patent coverage in the United States into 2039. ARCA has filed similar patent applications in other countries.
The FDA has issued a Special Protocol Assessment (SPA) agreement for a single Phase 3 clinical trial (PRECISION-AF) to examine Gencaro as a genetically targeted therapy for the prevention of AF recurrence in certain heart failure patients. We continue to evaluate the feasibility and potential timing for initiation of PRECISION-AF relative to the COVID-19 pandemic and the ability to recruit patients for a cardiovascular clinical trial.
Full Year 2020 Summary Financial Results

Cash and cash equivalents were $49.1 million as of December 31, 2020, compared to $8.4 million as of December 31, 2019. ARCA believes that its current cash and cash equivalents, together with the $23.3 million of net proceeds raised through February 2021 from sales of the common stock under the Company’s "at-the-market" offering, will be sufficient to fund its operations through 2022.

Research and development (R&D) expenses were $5.0 million for the year ended December 31, 2020, compared to $1.8 million for 2019. The $3.2 million increase in R&D expenses in 2020 as compared to 2019 was primarily related to the initiation of the rNAPc2 clinical trial in the second half of 2020. R&D expenses in 2021 are expected to be higher than 2020, as the Company continues the rNAPc2 Phase 2b clinical trial.

General and administrative (G&A) expenses were $4.8 million for the year ended December 31, 2020, compared to $4.0 million for 2019, an increase of approximately $0.8 million. The increase in expenses during 2020 was comprised primarily of increased legal and professional costs, insurance costs and higher personnel costs in 2020, as compared to 2019. G&A expenses in 2021 are expected to be consistent with those in 2020 as the Company maintains administrative activities to support our ongoing operations.

Total operating expenses for the year ended December 31, 2020 were $9.8 million compared to $5.8 million in 2019.

Net loss for the year ended December 31, 2020 was $9.7 million, or $2.07 per basic and diluted share, compared to $5.5 million, or $4.15 per basic and diluted share in 2019.

On March 18, 2021 Applied Therapeutics, Inc. (Nasdaq: APLT), a clinical-stage biopharmaceutical company developing a pipeline of novel drug candidates against validated molecular targets in indications of high unmet medical need, reported financial results for the fourth quarter and full year ended December 31, 2020 (Press release, Applied Therapeutics, MAR 18, 2021, View Source [SID1234576862]).

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"The fourth quarter was a productive period of internal planning and execution," said Shoshana Shendelman, PhD, Founder, CEO and Chair of the Board of Applied Therapeutics. "We are excited for what lies ahead in 2021, where our focus will be on advancing our late stage assets toward commercialization while initiating clinical development of our two new rare disease programs."

Recent Highlights

Announced Restart of Pediatric Galactosemia Study. In February 2021, the Company announced that the FDA lifted the clinical hold on the AT-007 ACTION-Galactosemia Kids pediatric clinical study, and the study resumed immediately. Applied Therapeutics worked closely with FDA to modify the trial, with the shared goal of ensuring that all patients have the opportunity to receive clinical benefit, and remains on target to submit an NDA no later than Q3 2021.

Announced the Launch of a Galactosemia Awareness and Education Initiative. Galactosemia Together is the first and only industry-led Galactosemia awareness and education campaign. Developed in partnership with the Galactosemia community, this initiative aims to address gaps in education by providing updated, reliable and credible resources to help connect, educate and support those families impacted by this disease.

Announced Magnetic Resonance Spectroscopy (MRS) Data from ACTION-Galactosemia Study. In December 2020, the Company shared MRS data on reduction of galactitol levels in the brain of Galactosemia patients treated with AT-007 in the ACTION-Galactosemia adult study. Overall, plasma reduction in galactitol correlated with brain reduction in galactitol. At the two doses which demonstrated statistically significant reduction in plasma galactitol, 20 and 40mg/kg, 3 out of 4 patients displayed substantial galactitol reduction ranging from 61.94% to 69.80% reduction from baseline.

Closed Public Offering of 3,000,000 Shares of Common Stock at a Price to the Public of $23.00 Per Share. In February 2021, the Company completed an underwritten public offering of 3,450,000 shares of common stock, including the exercise in full of the underwriters’ option to purchase 450,000 additional shares of common stock at a price of $23.00 per share, resulting in aggregate net proceeds of approximately $74.3 million.
Financial Results

Cash and cash equivalents and short-term investments totaled $96.8 million as of December 31, 2020, compared with $38.9 million at December 31, 2019. This does not include approximately $74.3 million in aggregate net proceeds the Company received from the underwritten public offering of common stock in February 2021.

Research and development expenses for the year ended December 31, 2020 were $61.8 million, compared to $32.4 million for the year ended December 31, 2019. The increase of $29.4 million related to an increase in clinical and pre-clinical expense of $11.3 million, primarily related to the progression of the AT-007 ACTION-Galactosemia adult extension and the AT-001 Phase 3 ARISE-HF clinical studies, as well as the commencement and progression of the AT-007 ACTION-Galactosemia Kids pediatric registrational study; an increase in drug manufacturing and formulation expenses of $15.4 million primarily related to the commencement of the 2020 manufacturing campaigns and the associated raw material deliveries and AT-007 and AT-001 drug product batch releases; an increase in personnel expenses of $0.6 million due to the increase in headcount in support of our clinical program pipeline; a decrease in stock-based compensation of $0.2 million due to the stock option modification expense recognized during the year ended December 31, 2019 for the acceleration of certain options vesting following the IPO; offset by an increase in expense recognized during the year ended December 31, 2020 due to new stock option and restricted stock grants; and an increase of regulatory and other expenses of $2.3 million primarily related to University of Miami license fees and increased clinical consulting fees recognized during the year ended December 31, 2020.

General and administrative expenses were $32.7 million for the year ended December 31, 2020, compared to $13.2 million for the year ended December 31, 2019. The increase of $19.4 million was an increase in professional and legal fees of $4.1 million due to increased operations and costs associated with being a public company for a full year; an increase of $5.7 million related to the establishment of a commercial department; an increase in personnel expenses of $4.2 million and an increase in stock-based compensation of $2.0 million due to an increase in headcount; an increase of insurance expenses of $1.8 million related to increased D&O insurance costs; and an increase in other expenses of $1.6 million, primarily relating to increased costs of rent and other office expenses.

Net loss for the year ended December 31, 2020 was $94.0 million, or $4.28 per basic and diluted common share, compared to a net loss of $45.5 million, or $3.55 per basic and diluted common share, for the year ended December 31, 2019.