On September 24, 2020 Monte Rosa Therapeutics, a biotechnology company focused on developing precision medicines to degrade disease-causing proteins, reported the closing of a Series B financing of $96 million (Press release, Monte Rosa Therapeutics, SEP 24, 2020, View Source [SID1234565584]). This financing will enable Monte Rosa to accelerate the growth of its pipeline, advance development candidates into the clinic and bolster its platform capabilities to rationally design and develop small molecule degraders (also known as molecular glues) that hijack the body’s innate ability to degrade proteins. Through this approach Monte Rosa Therapeutics will eradicate undruggable proteins that cause or drive the progression of genomically defined diseases intractable to standard care, including cancer.

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The Series B financing was led by Aisling Capital with participation from founding investor Versant Ventures and existing investor New Enterprise Associates. Additional new investors included HBM Healthcare Investments, Cormorant Asset Management, GV, Amzak Health, Casdin Capital, Sixty Degree Capital and Cambridge Asset Management.

"We are pleased to have the support of this strong group of investors who share our vision for driving a next-generation drug discovery approach that captures the promise of expanding the field of protein degradation into a broader array of diseases," said Markus Warmuth, M.D., CEO of Monte Rosa. "With this financing, we are now well positioned to broadly develop our integrated drug discovery platform and advance multiple new therapies toward clinical development."

The company has made robust progress since it was launched by Ridgeline, Versant’s Discovery Engine based in the Technologiepark Basel, in collaboration with The Institute of Cancer Research (ICR), London, and Cancer Research UK, with academic co-founders Professor Ian Collins, Ph.D., Head of Chemistry at ICR – who continues to lead an active collaboration with Monte Rosa – and former ICR Professor Rajesh Chopra, M.D., both thought leaders in the field of protein degradation.

In connection with the Series B round, the company also announced that Andrew Schiff, M.D., of Aisling Capital, and Chandra P. Leo, M.D., of HBM Partners, will join its Board of Directors. They join existing board members Dr. Warmuth; Brad Bolzon, Ph.D., and Alex Mayweg, Ph.D., of Versant; Ali Behbahani, M.D., of NEA; and Kim Blackwell, M.D., of Tempus Labs, Inc.

"Many approved drugs have been developed to inhibit a protein’s function. Monte Rosa’s goal is to eliminate the protein altogether," said Dr. Schiff. "This investment will continue to support the experienced team led by Markus and will enable the company to target known drivers of cancers and other diseases that are currently unaddressed with conventional methods."

"Monte Rosa has built one of the largest and highly focused libraries of small molecule protein degraders that target critical disease drivers," said Dr. Mayweg, Chair of the Board of Directors. "The company is now poised to bring forward multiple drug candidates for some of the most difficult-to-treat cancers and other diseases."

On September 24, 2020 TriSalus Life Sciences (TriSalus), an emerging immuno-oncology company committed to transforming outcomes for patients with solid tumors, reported its therapeutic clinical development strategy following the successful acquisition of SD-101, an investigational IND-ready immunotherapy, from Dynavax Technologies on August 3, 2020 (Press release, TriSalus Life Sciences, SEP 24, 2020, View Source [SID1234565583]).

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SD-101 is an investigational toll-like receptor 9 (TLR9) agonist that has been tested in Phase 2 clinical trials for advanced cutaneous melanoma and head and neck cancer, evaluating efficacy, safety, and the ability to increase responsiveness to checkpoint inhibitors in PD-L1 negative tumors. By combining SD-101 with TriSalus’ proprietary FDA cleared, drug delivery technologies, TriSalus will deliver the agent into the local vasculature of solid tumors. The Company intends to begin evaluating SD-101 in patients with uveal melanoma liver metastases followed by testing in patients with pancreatic ductal adenocarcinoma and colorectal cancer liver metastases. In addition, a separate program for locally advanced pancreatic ductal adenocarcinoma is in progress.

Mats Wahlstrom, Chairman of TriSalus Life Sciences, commented, "Our strategy is to develop a portfolio of immuno-oncology therapeutics and innovative infusion technologies to solve the two key reasons for poor outcomes in pancreatic and liver solid tumors ─ immunosuppression and low therapeutic index. The recent acquisition of SD-101 is a strong start to our therapeutics portfolio strategy. We plan to deploy multiple approaches with SD-101 by testing it clinically in a range of liver and pancreatic cancers for which few options currently exist."

Mary Szela, Chief Executive Officer and President of TriSalus Life Sciences, added, "SD-101 represents an important component of the clinical program, studying the safety and effectiveness on activation of the immune system to help attack solid tumors. Building on the acquisition of our first therapeutic candidate, we will seek other immuno-oncology products which could benefit from being delivered directly into the disease site through acquisitions, licenses, and partnerships."

Steven Katz, MD, Chief Medical Advisor of TriSalus and Chairman of its Scientific Advisory Board, said, "As an investigational TLR9 agonist, SD-101 has shown promising immunostimulatory capabilities that promote anti-tumor activity in Phase 1b/2 clinical studies.1 By using Pressure-Enabled Drug Delivery, (PEDD), for intravascular, regional, rather than systemic delivery, our intent is to increase SD-101’s therapeutic index. Our clinical development program will initially evaluate SD-101 delivered with PEDD for treatment of uveal melanoma liver metastases. Concurrently, we will develop three additional programs assessing a combination of SD-101 and other immuno-oncology agents delivered with PEDD."

Richard Carvajal, MD, Director of Experimental Therapeutics and Director of the Melanoma Service at Columbia University Medical Center, concluded, "Based on the biology of uveal melanoma and the clinical results in cutaneous melanoma, delivery of TLR9 agonists into the liver has been quite challenging. I am excited about studying the combination of TriSalus’ delivery technology with SD-101 in uveal melanoma liver metastases."

The Company reported that it will seek a meeting with the Food and Drug Administration to share study designs and clinical plans for the initiation of human clinical studies in uveal melanoma liver metastases, the most common primary intraocular malignancy in adults, representing approximately 85% of all ocular melanomas.2

TriSalus was formed to investigate treatments to help stimulate the immune system to overcome immunosuppression by delivering a combination of immuno-oncology therapies directly to the site of disease. Trisalus is researching this multi-pronged approach to reprogram the immunosuppressive tumor microenvironment, harness the power of tumor killing agents, and deliver these therapies directly to the tumor through its Pressure-Enabled Drug Delivery (PEDD) approach. The Company has identified validated, IND-ready targets to acquire through license agreements, collaborations, or joint ventures. TriSalus is initially focused on the goal of successfully treating intractable solid tumors including uveal melanoma liver metastases and pancreatic cancer.

About SD-101

SD-101 is an investigational proprietary short sequence of synthetic deoxyribonucleic acid (DNA) which binds to the Toll-Like receptor 9 (TLR9) found on suppressive immune cells including myeloid-derived suppressor cells and antigen presenting cells.3 SD-101 has been evaluated in numerous clinical studies to assess safety and efficacy. Investigational studies suggest responsiveness to checkpoint inhibitors in PD-L1 negative tumors as well as inducing an influx of cytotoxic T cells and interferon gamma production.1

SD-101 will be evaluated in multiple visceral organ tumor types to assess its safety and activity via PEDD as well as in combination with other immunotherapies and modalities. For more information on SD-101 clinical trials that are currently recruiting patients, please visit www.clinicaltrials.gov.

About Pressure-Enabled Drug Delivery (PEDD)

Pressure-Enabled Drug Delivery (PEDD) approach with SmartValve technology features a self-expanding, nonocclusive, one-way valve which can infuse therapeutics into solid tumor vasculature 4 The FDA cleared SmartValve devices have been shown to deliver more therapy into the tumor while preventing embolic reflux5.

On September 24, 2020 Eagle Pharmaceuticals, Inc. (Nasdaq: EGRX) ("Eagle" or the "Company") reported that its Board of Directors has approved a $25 million accelerated share repurchase ("ASR") transaction with JPMorgan Chase Bank, National Association ("JP Morgan") as part of the Company’s existing $160 million share repurchase program (Press release, Eagle Pharmaceuticals, SEP 24, 2020, View Source [SID1234565582]).

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The specific number of shares to be repurchased pursuant to the ASR is based on the average of the daily volume weighted average share prices of the Company’s common stock, less a discount, during the term of the ASR program. Based on yesterday’s closing price, the $25 million ASR would represent approximately 5% of the Company’s basic outstanding shares. Upon completion of the ASR, Eagle will have bought back a total of approximately $205 million of its stock since its IPO in 2014.

"The $25 million ASR reflects our ongoing confidence in our pipeline and continued earnings potential. With multiple opportunities to expand our RYANODEX franchise, the anticipated near-term launch of vasopressin, and three potential oncology launches in 2022 including PEMFEXY, fulvestrant and SM-88, along with the recent approval received by our Japanese marketing partner, SymBio, for its ready-to-dilute TREAKISYM product, we remain committed to building shareholder value," stated Scott Tarriff, Chief Executive Officer of Eagle Pharmaceuticals.

Under the terms of the agreement, Eagle will pay $25 million to JP Morgan on September 24, 2020, and receive 505,817 shares, representing approximately 80% of the notional amount of the ASR, based on the closing price of $39.54 on September 23, 2020. Upon settlement of the ASR, the final number of shares repurchased will be trued up based on the average of the daily volume weighted average share prices of the Company’s common stock, less a discount, during the term of the accelerated share repurchase program. Eagle expects the ASR to be completed in the fourth quarter of 2020. As of September 23, 2020, the Company had 13.5 million common shares outstanding.

The Company intends to use cash on hand to fund the ASR program. As of June 30, 2020, cash and cash equivalents were $108.2 million, net accounts receivable was approximately $46.8 million, and debt was $37 million.

On September 24, 2020 Molecular Partners AG (SIX: MOLN), a clinical-stage biotech company that is developing a new class of custom-built protein drugs known as DARPin therapeutics, reported the presentation of preclinical findings supporting the mechanism of MP0317, a tri-specific DARPin product candidate that includes binding domains for fibroblast activation protein (FAP), CD40, and human serum albumin (HSA) (Press release, Molecular Partners, SEP 24, 2020, View Source [SID1234565581]). The presentation, titled "Novel therapeutic design of tumor-targeted CD40 agonist DARPin molecule leads to antitumor activity with limited toxicity", will be presented today at 2pm (EDT) at the 11th Annual World Bispecific Summit by Clara Domke, a senior scientist oncology research at Molecular Partners.

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Data presented demonstrate that a mouse surrogate MP0317 molecule induces FAP-dependent activation of B cells, dendritic cells and macrophages. FAP is expressed on activated cancer associated fibroblasts (CAF) and is overexpressed in the stroma of many solid tumors. Since MP0317 only activates these immune cells in the presence of FAP, MP0317 may avoid the dose-limiting side effects historically associated with systemic administration of CD40 antibodies. Additionally, in a FAP-positive colorectal cancer model, MP0317 induced complete tumor responses and demonstrated induction of an anti-tumor immunological memory, protecting the mice against subsequent tumor challenges without the need for additional treatment.

"Potent and situationally-activated antitumor therapies are an important new area for cancer treatment, when systemic toxicity can limit effective dosing of therapies with proven mechanisms like CD40 activation. With MP0317 we are tackling multiple kinds of cancer where highly fibrous, FAP-rich stromal tissue has historically presented a barrier to immune cell penetration. These data demonstrate the potential for turning this barrier into a target, by utilizing it as an anchor for the delivery of super-potent immunostimulatory molecules," said Nicolas Leupin M.D., chief medical officer of Molecular Partners. "We look forward to filing appropriate regulatory applications for MP0317 around the end of 2020 and initiating clinical studies in the first half of 2021."

The presentation will be made available on the company’s corporate website, www.molecularpartners.com.

About Molecular Partners’ Oncology Portfolio
DARPin therapeutic candidates are uniquely versatile, custom-built molecules with the potential to help people suffering from a broad range of diseases, including cancer. Given their small size, multi-functional design and unique binding surfaces, DARPin molecules can address molecular targets that have been difficult to access by other drug modalities, such as antibodies. Molecular Partners has delivered substantial proof-of-concept in its oncology portfolio by advancing investigational DARPin therapeutics against highly validated targets such as HER2, HGF and VEGF into clinical studies. The Company has focused the next phase of its oncology portfolio strategy on exploring targets with novel mechanisms for selective and site-specific immune cell activation. Molecular Partners has designed DARPin candidates to activate only when proximal to the target tumor, improving efficacy and potentially eliminating systemic off-target side effects. Promising immune modulators such as peptide-MHC complexes, 4-1BB and CD40 are also the target of novel DARPin programs. Further, DARPin approaches are applied to novel targets such as peptide MHC-complexes.

On September 24, 2020 MediciNova, Inc., a biopharmaceutical company traded on the NASDAQ Global Market (NASDAQ:MNOV) and the JASDAQ Market of the Tokyo Stock Exchange (Code Number: 4875), reported positive clinical findings published in Cancer Chemotherapy and Pharmacology regarding MN-166 (ibudilast) as a treatment for prevention of chemotherapy-induced peripheral neuropathy (CIPN) (Press release, MediciNova, SEP 24, 2020, View Source [SID1234565580]).

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The publication, entitled "Ibudilast for prevention of oxaliplatin-induced acute neurotoxicity: a pilot study assessing preliminary efficacy, tolerability, and pharmacokinetic interactions in patients with metastatic gastrointestinal cancer", is the result of a collaborative effort between MediciNova and Dr. Janette Vardy, Professor of Cancer Medicine, University of Sydney Concord Cancer Centre in Australia. The authors report that co-administration of MN-166 (ibudilast) with oxaliplatin resulted in improvement or stabilization of oxaliplatin-induced neurotoxicity in the majority of participants treated with oxaliplatin.

This prospective, open-label, sequential crossover study was conducted to assess whether MN-166 (ibudilast) can reduce acute peripheral neuropathy symptoms in patients with metastatic upper gastrointestinal or colorectal cancer. A total 16 patients consented, and 14 patients completed two cycles of oxaliplatin-containing chemotherapy, one cycle with conventional chemotherapy (Cycle A) and one cycle of chemotherapy with concurrent MN-166 treatment (Cycle B). As a cross-over design, each participant acted as their own control. Participants underwent a number of assessments for neurotoxicity on Day 3 of each cycle, and at the completion of each cycle, including the Oxaliplatin-Specific Neurotoxicity Scale (OSNS), the Total Neuropathy Score Clinical (TNSc), the Functional Assessment of Cancer Therapy/Gynaecologic Oncology Group—Neurotoxicity (FACT/GOG-Ntx13), and the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) neuropathy subscale.

Major findings from the publication are as follows:

Across all neurotoxicity measures, a majority of participants experienced either an improvement or no worsening of neurotoxicity with MN-166 (ibudilast) treatment
According to OSNS assessments, 12 out of 14 participants reported acute neurotoxicity (Grade 1 or 2) in both cycles. Of those, 10 out of 12 participants were unchanged and 2 participants had improved symptoms from Grade 2 to Grade 1 with MN-166 (ibudilast) co-treatment.
According to score changes with FACT/GOG-Ntx13, TNSc and NCI-CTCAE, a majority of participants had no worsening of scores at the Day 3 and end of cycle time-points for Cycle B compared to Cycle A.
Pharmacokinetic analysis indicated no effect of MN-166 (ibudilast) on systemic exposure of oxaliplatin.
Yuichi Iwaki, M.D., Ph.D., President and Chief Executive Officer of MediciNova, Inc., commented, "We are very pleased to report positive results from this study. Acute neurotoxicity, which predicts chronic CIPN, usually recurs with oxaliplatin chemotherapy and in most cases, patients experience worsening of neurotoxicity symptoms with continued chemotherapy. What makes this remarkable is that half of participants reported improved symptoms in the acute period and showed improved neurological parameters on clinical assessment with ibudilast treatment."

About Chemotherapy-induced Peripheral Neuropathy

Peripheral neuropathy is a set of symptoms caused by damage to the nerves that are outside of the brain and spinal cord. These distant nerves are called peripheral nerves. Some of the chemotherapy and other drugs used to treat cancer can damage peripheral nerves that carry sensations to the hands and feet. This damage results in chemotherapy-induced peripheral neuropathy (CIPN) and is a common side effect of cancer chemotherapy. Most commonly, people complain of "pins and needles" in their toes and fingers. CIPN may affect cancer outcomes due to reductions in chemotherapy dosing and/or premature treatment discontinuation and have a profound impact on quality of life and survivorship. According to a meta-analysis which included more than 4,000 patients, CIPN prevalence was 68% when measured in the first month after chemotherapy, 60% at 3 months, and 30% at 6 months or more (Seretny et al., 2014). Long-term neurotoxicity is an important issue for the growing number of cancer survivors, with the highest number of affected patients having been treated for breast and/or colon cancer.

About MN-166 (ibudilast)

MN-166 (ibudilast) is a first-in-class, orally bioavailable, small molecule macrophage migration inhibitory factor (MIF) inhibitor and phosphodiesterase (PDE) -4 and -10 inhibitor that suppresses pro-inflammatory cytokines and promotes neurotrophic factors. Our earlier human studies demonstrated significant reductions of serum MIF level after treatment with MN-166 (ibudilast). It also attenuates activated glial cells, which play a major role in certain neurological conditions. MN-166 (ibudilast)’s anti-neuroinflammatory and neuroprotective actions have been demonstrated in preclinical and clinical studies, which provide the rationale for treatment of amyotrophic lateral sclerosis (ALS), progressive multiple sclerosis (MS) and other neurological diseases such as glioblastoma (GBM), and substance abuse/addiction. MediciNova is developing MN-166 for ALS, progressive MS and other neurological conditions such as degenerative cervical myelopathy (DCM), glioblastoma, substance abuse/addiction, and chemotherapy-induced peripheral neuropathy, as well as prevention of acute respiratory distress syndrome (ARDS) caused by COVID-19. MediciNova has a portfolio of patents which covers the use of MN-166 (ibudilast) to treat various diseases including ALS, progressive MS, and drug addiction.