On March 16, 2021 Merck KGaA, Darmstadt, Germany, a leading science and technology company, reported topline data from the Phase II INTR@PID BTC 047 study evaluating bintrafusp alfa as a monotherapy in the second-line treatment of patients with locally advanced or metastatic biliary tract cancer (BTC) who have failed or are intolerant of first-line platinum-based chemotherapy (Press release, Merck KGaA, MAR 16, 2021, View Source [SID1234576753]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

In the study of 159 patients, bintrafusp alfa demonstrated single-agent efficacy and durability with a manageable safety profile after more than nine months of follow-up, with an Independent Review Committee (IRC)-adjudicated objective response rate (ORR) of 10.1% (95% CI: 5.9% to 15.8%) per RECIST 1.1. Though single-agent activity was observed, the study did not meet the pre-defined threshold that would have enabled regulatory filing for BTC in the second line setting. The results will be submitted for presentation at an upcoming medical meeting or publication.

"Given the high unmet treatment need in BTC, where single agent immunotherapy in PD-L1 all comers has shown an ORR of 5.8%, we are encouraged by the single agent clinical activity of bintrafusp alfa in this study as a second-line treatment," said Milind Javle, MD, professor of GI medical oncology, MD Anderson Cancer Center, and an investigator for the INTR@PID BTC 047 study. "The bintrafusp alfa 047 study is one of the most important clinical investigations conducted for chemo-refractory biliary cancers, and I would like to thank the patients, families, and study team for their valuable participation."

"This study demonstrates single-agent activity with bintrafusp alfa in locally advanced or metastatic BTC, a disease that has been historically difficult to treat," said Danny Bar-Zohar, M.D., Global Head of Development for the Healthcare business sector of Merck KGaA, Darmstadt, Germany. "The data will contribute to our understanding of addressing both TGF-β and PD-L1 inhibition in the tumor microenvironment."

A Phase II/III study of bintrafusp alfa in combination with chemotherapy as a first-line treatment for BTC (INTR@PID BTC 055), which is assessing a different hypothesis than the second-line monotherapy study, has completed enrollment in the Phase II portion and is currently ongoing.

*Bintrafusp alfa is currently under clinical investigation and not approved for any use anywhere in the world.

About Biliary Tract Cancer (BTC)

BTCs are a group of rare, aggressive gastrointestinal cancers associated with poor outcomes and limited treatment options. There is currently no globally accepted standard of care in the second-line setting and chemotherapy as well as immunotherapies have demonstrated low response rates in BTC. Epithelial-to-mesenchymal transition (EMT), a hallmark of tumor progression and drug resistance, plays an important role in BTC, and has been shown to be triggered by TGF-β signaling.

About Bintrafusp Alfa

Bintrafusp alfa (M7824), discovered in-house at Merck KGaA, Darmstadt, Germany, and currently in clinical development through a strategic alliance with GSK, is a potential first-in-class investigational bifunctional fusion protein designed to simultaneously block two immunosuppressive pathways, TGF-β and PD-L1, within the tumor microenvironment. This bifunctional approach is thought to control tumor growth by potentially restoring and enhancing anti-tumor responses. In preclinical studies, bintrafusp alfa has demonstrated antitumor activity both as monotherapy and in combination with chemotherapy. Based on its mechanism of action, bintrafusp alfa offers a potential targeted approach to addressing the underlying pathophysiology of difficult-to-treat cancers.

About the INTR@PID Clinical Trial Program

INTR@PID is a global clinical trial program investigating the potential co-localized, dual inhibition of TGF-β and PD-L1 with bintrafusp alfa (M7824) in multiple tumor types. Current clinical trial information can be found on the INTR@PID website at www.intrapidclinicaltrials.com. To date, globally more than 1,300 patients with various types of solid tumors have received bintrafusp alfa in the INTR@PID clinical development program.

The INTR@PID clinical development strategy is comprehensive and is pursuing non-redundant hypotheses grounded in preclinical and early clinical data findings that continue to be explored and may yield clinically meaningful insights to patients in need, including exploring settings where simultaneous, synchronized targeting of TGF-β and PD-L1 may offer the key to expanding the potential of immunotherapy; focusing on opportunities where PD-1/PD-L1 has suboptimal clinical activities and pathogenesis linked to TGF-β biology; and targeting specific tumors with biomarkers with a strong link to TGF-β signaling pathway.

All Merck KGaA, Darmstadt, Germany, press releases are distributed by e-mail at the same time they become available on the EMD Group Website. In case you are a resident of the USA or Canada please go to www.emdgroup.com/subscribe to register for your online subscription of this service as our geo-targeting requires new links in the email. You may later change your selection or discontinue this service.

On March 16, 2021 Merck (NYSE: MRK), known as MSD outside the United States and Canada, reported that the U.S. Food and Drug Administration (FDA) has accepted and granted priority review for a New Drug Application (NDA) for the hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor belzutifan (pronounced bell-ZOO-ti-fan), a novel investigational candidate in Merck’s oncology pipeline, for the potential treatment of patients with von Hippel-Lindau (VHL) disease-associated renal cell carcinoma (RCC), not requiring immediate surgery (Press release, Merck & Co, MAR 16, 2021, View Source [SID1234576713]). This NDA is based on data from the Phase 2 Study-004 trial, in which belzutifan showed a confirmed overall response rate of 36.1% (n=22/61) (95% CI: 24.2-49.4) in patients with VHL disease-associated RCC. The FDA has set a Prescription Drug User Fee Act (PDUFA), or target action, date of September 15, 2021.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Von Hippel-Lindau disease is a rare genetic condition for which there is no systemic treatment option available and is associated with a high risk of cancer development in multiple organs. In fact, up to 70% of patients with VHL develop renal cell carcinoma during their lifetime," said Dr. Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories. "This priority review validates the important progress we have made to expand and diversify Merck’s oncology pipeline with innovative, new therapeutic approaches. We look forward to working closely with the FDA to bring belzutifan to patients in need."

Merck is also studying belzutifan in advanced RCC and other tumor types through a broad clinical program. In addition to the ongoing Phase 2 Study-004 trial, belzutifan is being evaluated in Phase 3 trials as monotherapy and as part of a combination regimen in previously treated patients and as part of a combination regimen as a first-line treatment for advanced clear cell RCC.

About the Phase 2 Study-004 Trial

This application is based on data from Study-004 (ClinicalTrials.gov, NCT03401788), which is a Phase 2, open-label trial evaluating belzutifan for the potential treatment of patients with VHL disease who had at least one measurable solid tumor localized to the kidney and who did not require immediate surgery. The study enrolled 61 patients who received belzutifan 120 mg orally once daily until disease progression or unacceptable toxicity. The primary endpoint was objective response rate in VHL disease-associated RCC. Secondary endpoints in RCC tumors include disease control rate, duration of response, time to response, progression-free survival, time to surgery and safety.

Additionally, this study evaluated response rates in other common VHL disease-associated tumors, including pancreatic cysts, pancreatic neuroendocrine tumors, central nervous system (CNS) hemangioblastomas, and retinal hemangioblastomas.

About Belzutifan

Belzutifan (MK-6482) is a novel, potent and selective inhibitor of HIF-2α. Proteins known as hypoxia-inducible factors, including HIF-2α, can accumulate in patients when VHL, a tumor-suppressor protein, is inactivated. If not properly regulated, the accumulation of HIF-2α can stimulate several oncogenes associated with cellular proliferation, angiogenesis and tumor growth, leading to the growth of both benign and malignant tumors. This inactivation of VHL has been observed in more than 90% of clear cell RCC tumors. Research into VHL biology that led to the discovery of HIF-2α was awarded the Nobel Prize in Physiology or Medicine in 2019.

About Von Hippel-Lindau Disease and Renal Cell Carcinoma

Von Hippel-Lindau disease is a rare genetic disease that affects one in 36,000 people (200,000 cases worldwide and 10,000 cases in the U.S. alone). Patients with VHL disease are at risk for benign blood vessel tumors as well as several cancers, including RCC. As many as 70% of people with VHL disease develop RCC.

Renal cell carcinoma is by far the most common type of kidney cancer; about nine of 10 kidney cancers are RCCs, and about seven of 10 RCCs are clear cell. Worldwide, it is estimated there were nearly 431,300 cases of kidney cancer diagnosed and almost 179,400 deaths from the disease in 2020. In the U.S. alone, it is estimated there will be almost 76,100 new cases of kidney cancer diagnosed and nearly 13,800 deaths from the disease in 2021.

Merck’s Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

On March 11, 2021 Prelude Therapeutics Inc. ("Prelude", "the Company", "we", "our") (Nasdaq: PRLD), a clinical-stage precision oncology company, reported its financial results for the fourth quarter and full year ended December 31, 2020 and provided an update on recent developments (Press release, Prelude Therapeutics, MAR 16, 2021, View Source [SID1234576737]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"2020 marked a highly transformational year for Prelude with the successful completion of an initial public offering and progress across our three clinical-stage programs," said Kris Vaddi, PhD, Chief Executive Officer of Prelude Therapeutics. "We are firmly committed to bringing novel therapies to patients in areas of high unmet need, and we have entered 2021 with both the momentum and resources that we believe will carry us through several key milestones. Notably, we are pleased to announce the completion of dose escalation activities in our ongoing Phase 1 trial of PRT543, our lead PRMT5 inhibitor, in patients with advanced solid tumors and hematologic malignancies, and that we will soon begin initiating additional expansion cohorts. We look forward to sharing clinical data for this program, as well as for our second PRMT5 inhibitor, PRT811, in the second half of this year."

Dr. Vaddi added, "The ongoing Phase 1 trial of our third clinical candidate, PRT1419, an MCL1 inhibitor, also continues to progress, with the addition of dose expansion cohorts expected in the second half of the year. Finally, the continued advancement of our preclinical programs remains a high priority for us in 2021, with the anticipated submission of an IND application for PRT2527, our CDK9 inhibitor, in the second half of this year."

Recent Highlights and Upcoming Milestones

PRT543

Phase 1 Dose Escalation Complete; Additional Expansion Cohorts to Open in the Second Quarter. The Company reported that the dose escalation portion of the Phase 1 trial of its lead product candidate, PRT543, is now complete, and that a recommended expansion dose with adequate safety, pharmacokinetics, and target engagement profile has been established. PRT543 is designed to be a potent, selective, and oral inhibitor of PRMT5. The dose expansion portion of the Phase 1 trial is currently open for the patient cohort with adenoid cystic carcinoma, and will be open for additional patient cohorts with solid tumor and hematologic malignancies early in the second quarter. As previously announced, preliminary data from the dose escalation portion of the trial demonstrated early signs of clinical activity and tolerability. The Company anticipates presenting initial clinical data from the Phase 1 trial at medical meetings in the second half of 2021.

Preclinical Data to be Featured at the 2021 AACR (Free AACR Whitepaper) Annual Meeting. Three preclinical presentations on PRT543 will be featured at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting being held April 10-15, 2021 in a virtual setting. A copy of the posters, titled "PRMT5 inhibition downregulates MYB and NOTCH1 signaling, key molecular drivers of adenoid cystic carcinoma" (abstract 1138), "PRMT5 inhibition epigenetically regulates DNA damage response pathways in cancer cells and sensitizes to chemotherapy and PARP inhibition" (abstract 1185), and "PRMT5 inhibition regulates alternative splicing and DNA damage repair pathways in SF3B1 R625C expressing uveal melanoma cells" (abstract 1137), will be available in the Publications section of the Prelude Therapeutics website following the conclusion of the meeting.
PRT811

Phase 1 Dose Expansion Cohorts Expected to Commence in Mid-2021. The dose escalation portion of the Company’s Phase 1 trial of its second clinical product candidate, PRT811, which is designed to be a potent, selective, and brain penetrant PRMT5 inhibitor, in patients with advanced solid tumors, including glioblastoma multiforme (GBM), remains ongoing. As previously reported, the trial has demonstrated early signs of clinical activity and tolerability. Prelude remains on track to establish the recommended expansion dose and commence the dose expansion portion of the trial in mid-2021 in patients with central nervous system cancers including GBM, with initial clinical data expected by the end of 2021.
PRT1419

Oral Formulation: Dose Expansion and Combination Cohorts Expected to be Added to Ongoing Phase 1 Trial in the Second Half of 2021. The dose escalation portion of the Company’s first-in-human Phase 1 open-label, multicenter, dose-escalation study of oral PRT1419 in patients with relapsed/refractory hematologic malignancies, including acute myeloid leukemia and high-risk myelodysplastic syndromes, remains ongoing. PRT1419, which is the Company’s third clinical candidate, is designed to be an orally available, potent, and selective MCL1 inhibitor. The Company expects to add dose expansion and combination cohorts to the Phase 1 clinical trial in the second half of 2021.

IV Formulation: IND Application Cleared. Prelude reported the recent U.S. Food and Drug Administration (FDA) clearance of the Company’s Investigational New Drug (IND) application for an intravenous (IV) formulation of PRT1419. A Phase 1 trial of the IV formulation, which leverages the optimized physicochemical properties of PRT1419, is expected to commence in the first half of 2021 in patients with solid tumors.

Data on Preclinical Characterization to be Featured at the 2021 AACR (Free AACR Whitepaper) Annual Meeting. Data on the preclinical characterization of PRT1419 will be featured during a poster session at the 2021 AACR (Free AACR Whitepaper) Annual Meeting. A copy of the poster, titled "Preclinical characterization of PRT1419, a potent, selective and orally available inhibitor of MCL1" (abstract 983), will be available in the Publication section of the Prelude Therapeutics website following the conclusion of the meeting.
Discovery Programs

Advancement of Earlier-Stage Candidates Expected in 2021. Prelude remains on track to submit an IND application for PRT2527, which is designed to be a potent and selective CDK9 inhibitor, in 2021. The Company also continues to expect to initiate IND-enabling studies for PRT-SCA2, which is designed to be a SMARCA2 protein degrader, in 2021.

Preclinical Data on SMARCA2 Protein Degradation to be Featured at the 2021 AACR (Free AACR Whitepaper) Annual Meeting. A poster presentation on Prelude’s SMARCA2 protein degradation program, titled "Potent SMARCA2 targeted degraders induce genetic synthetic lethality in SMARCA4 deleted cancer" (abstract 1139), will be presented at the 2021 AACR (Free AACR Whitepaper) Annual Meeting. A copy of the poster will be available in the Publications section of the Prelude Therapeutics website following the conclusion of the meeting.
Corporate

Completed Successful Upsized Public Offering of $172.5 Million. In January 2021, the Company announced the closing of its upsized public offering of 2,583,334 shares of its voting common stock and 291,666 shares of its non-voting common stock, each at a public offering price of $60.00 per share, which includes the exercise in full of the underwriters’ option to purchase an additional 375,000 shares of its voting common stock. The aggregate gross proceeds from this offering were $172.5 million, before deducting underwriting discounts and commissions and estimated offering expenses payable by Prelude.
Fourth Quarter and Full Year 2020 Financial Results

Cash and Cash Equivalents: Cash and cash equivalents as of December 31, 2020 were $218.3 million.

Research and Development (R&D) Expenses: For the fourth quarter of 2020, R&D expense increased to $14.6 million from $8.8 million for the prior year period, and for the full year increased to $48.2 million compared to $24.3 million for 2019. The fourth quarter and full year increases were primarily due to increased clinical research costs for the PRT543 and PRT811 clinical trials and increased costs associated with the initiation of the clinical trial for PRT1419, which began in the third quarter of 2020. The Company also incurred an increase in chemistry, manufacturing, and other costs for those trials.

General and Administrative (G&A) Expenses: G&A expenses for the fourth quarter of 2020 increased to $4.9 million from $1.2 million for the prior year period, and for the full year increased to $10.6 million compared to $3.8 million for 2019. The fourth quarter and full year increases were primarily due to an increase in personnel related expense due to increased employee headcount and an increase in professional fees as the Company expanded its operations to support R&D efforts and incurred additional costs associated with operating as a public company.

Net Loss: For the fourth quarter of 2020, net loss was $19.3 million, or $0.45 per share, compared with a net loss of $10.0 million, or $5.56 per share, for the same period in 2019. Net loss for the year ended December 31, 2020 was $56.9 million, or $4.56 per share, compared with a net loss of $27.6 million, or $16.52 per share, for the year ended December 31, 2019.

Financial Guidance: The Company believes that its current cash and cash equivalents will be sufficient to fund operating expenses and capital expenditure requirements into 2023.

On March 16, 2021 PEP-Therapy, a biotechnology company developing cell penetrating peptides as targeted therapies in oncology, and Institut Curie, France’s leading cancer center, reported that they have been granted approval from the French National Agency for Medicines and Health Products (ANSM) to proceed with the first-in-human clinical trial of PEP-Therapy’s lead drug candidate, PEP-010 (Press release, PEP-Therapy, MAR 16, 2021, View Source [SID1234576754]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

PEP-010 is a first-in-class therapeutic peptide based on PEP-Therapy’s innovative Cell Penetrating and Interfering Peptides (CP&IP) technology. These innovative molecules penetrate cells and specifically block relevant intracellular protein-protein interactions, leading to the inhibition of key pathological mechanisms, without altering physiological mechanisms. PEP-010 is a pro-apoptotic agent which has demonstrated anti-tumor efficacy in a number of pre-clinical models and a good safety profile.

The clinical trial, named ‘CleverPeptide’, is an open-label, non-controlled, multicenter, dose escalation, Phase I clinical trial with an expansion Phase. This Phase Ia/b study has been designed to evaluate the safety, tolerability, pharmacokinetics and preliminary antitumor activity of intravenous PEP-010, administered as a single agent and in combination with paclitaxel in patients with recurrent and/or metastatic solid tumors, and in particular in Triple Negative Breast Cancer (TNBC) and Ovarian Cancer (OC).

This study is sponsored by Institut Curie and led by Pr. Christophe Le Tourneau, Medical Oncologist at Institut Curie and Head of Department of Drug Development and Innovation (D3i), and Principal Investigator of the trial.

Antoine Prestat, CEO and co-founder of PEP-Therapy said: "We are pleased to have been granted approval by ANSM to start this first-in-human clinical trial of PEP-010. This is a major milestone for PEP-Therapy and our partners, amongst which Institut Curie and Sorbonne University where our technology originated from. PEP-010 aims to fight cancers with poor prognosis for which there are only few or no therapeutic alternatives. We look forward to starting this trial in the coming weeks and to generating results that we hope will confirm the promising results seen in preclinical studies."

"This exciting step has been achieved through a strong collaboration between PEP-Therapy and Institut Curie since its inception, demonstrating the ability to develop innovative therapeutics emerging from French institutional research. I am very pleased to involve the D3i – Department of Drug Development and Innovation – in this clinical trial", says Pr Christophe Le Tourneau.

The study will be conducted in three clinical centers in France: Institut Curie, Gustave Roussy and the François Baclesse Center.

On March 16, 2021 Selvita S.A. [ticker: WSE: SLV] – one of the largest preclinical contract research organizations in Europe, reported that was named the Stock Company of the Year as a result of a competition organized by "Puls Biznesu" – one of the largest business daily in Poland. Selvita also won in two other categories: "The Board Competencies" and "Development Perspectives (Press release, Selvita, MAR 16, 2021, View Source;utm_medium=rss&utm_campaign=selvita-named-the-stock-exchange-company-of-the-year [SID1234576714])."

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

It was the 22nd edition of the competition, which is the oldest and the most prestigious ranking in the Polish capital market. Every year 100 professionals choose the best company. The jury consists of market analysts, investment advisers and managers, institutional investors, and securities house representatives. These experts measure companies in five categories: the management board competencies, success, products and services innovation, investor relations, and development perspectives.

Selvita’s success is spectacular, considering the fact that 2020 was the first full year when the company was listed on the Warsaw Stock Exchange as an independent entity.