On January 13, 2020 Curis, Inc (NASDAQ: CRIS) and DarwinHealth, Inc. reported a multi-year scientific research collaboration to use quantitative, systems biology-based algorithms, CLIA-approved technologies, and novel, validated approaches focused on Master Regulator (MR) proteins and tumor checkpoints to: (a) better understand and articulate the role of MYC in fimepinostat’s mechanism of action; and (b) explore additional potential novel biomarkers that may help patient selection in hematologic and solid tumors clinical studies (Press release, Curis, JAN 13, 2020, View Source [SID1234553071]).

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The collaboration will deploy DarwinHealth’s proprietary compound-checkpoint-tumor subtype matching platform, its VIPER algorithm to characterize protein activity signatures that are the hallmark of regulatory network dysfunction in cancer cells, and its high-throughput drug perturbation and Plate-Seq discovery platform to analyze the potential therapeutic efficacy of fimepinostat (a synthetic, orally-available, small molecule that inhibits the activity of histone deacetylase, or HDAC, and phosphatidyl-inositol 3 kinase, or PI3 kinase enzymes) across a number of tumor subtypes.

"The aim of this exciting collaboration," explained Professor Andrea Califano, Clyde and Helen Wu Professor and Chair, Department of Systems Biology, Columbia University and co-founder of DarwinHealth, "is to assess and characterize the role of MYC as a critical effector of fimepinostat activity in DLBCL, as well as its overall, tumor-specific Mechanism of Action (MoA), considering that both HDAC and PI3K inhibitors have been independently characterized among the strongest regulators of tumorigenic MYC activity. Additionally, the collaboration will mechanistically characterize additional therapeutic opportunities for fimepinostat across multiple hematopoietic and solid tumor subtypes, as selected by Curis for this scientific collaboration. The study will leverage the VIPER algorithm to characterize fimepinostat’s activity against key Master Regulator (MR) protein modules (tumor checkpoints) necessary for subtype-specific tumor viability."

As part of this initiative, DarwinHealth will provide a comprehensive readout of fimepinostat’s potential clinical value across a number of cancer tissue-specific contexts, including its genome-wide mechanism of action, its tumor-specific biomarkers of sensitivity and resistance, and its ability to synergize with venetoclax for combination therapy applications in DLBCL and solid tumors. Through quantitative modeling, mechanism-driven and biomarker-driven developmental trajectories for fimepinostat will be predicted to help Curis design in vivo validation studies and focused clinical studies to leverage key opportunities for this dual HDAC/PI3 kinase inhibitor that would not be apparent using conventional technologies.

"In light of promising clinical data already reported for fimepinostat, and its unique MOA, our Compound-2-Clinic (C2C) collaboration with Curis promises to be one of our most productive scientific collaborations," noted Dr. Gideon Bosker, CEO and co-founder of DarwinHealth. "Our C2C technologies are ideally suited to identify mechanistic alignment between compounds and cancer patients, based on their ability to inactivate the patient-specific master regulator proteins that are necessary for tumor state maintenance. Compounds and compound combinations prioritized by this technology can be efficiently validated, first in PDX models and subsequently in the clinic, using our NYS State, CLIA-certified DarwinOncoTreat/Target tests. In addition to achieving a more mechanistic characterization of MYC as a critical effector of fimepinostat activity in DLBCL, our goal is to delineate the range of additional tumor subtypes—many of which may be entirely unanticipated—where fimepinostat may consistently and predictably collapse tumor checkpoint activity, thus abrogating tumor growth. These discoveries can be quickly matured to precision, biomarker-driven, clinical human testing and commercial development."

"This scientific collaboration aligns with our development path for fimepinostat by deepening our understanding of the MYC mechanism of action and potentially identifying additional, novel trajectories, indications, mechanisms, and precision-focused drug-tumor alignments that can produce a more inclusive developmental roadmap for our lead compound," said James Dentzer, President and Chief Executive Officer of Curis. "The DarwinHealth team led by Drs. Andrea Califano and Mariano Alvarez, who co-developed VIPER technology in the Califano Lab at Columbia University, bring world-class expertise that will be invaluable for identifying the full commercialization pathway for fimepinostat."

"DarwinHealth’s approach to tumor checkpoint elucidation, linked to MR proteins, will help support fimepinostat’s MYC-driven mechanism of action," said Dr. Robert Martell, Head of R&D at Curis. "This approach is also ideally suited for identifying additional biomarkers in our DLBCL program and illuminating additional tumor subtypes in which fimepinostat, alone or in combination with venetoclax, may have therapeutic potential. These mechanistically relevant insights will help us to focus on, test, and prioritize with a higher likelihood of success, the comprehensive translational roadmap for fimepinostat in targeted clinical contexts."

As part of this collaboration, DarwinHealth will be eligible for milestone payments and royalties for applications that directly result from their analyses.

On January 13, 2020 Constellation Pharmaceuticals presented the corporate presentation (Presentation, Constellation Pharmaceuticals, JAN 13, 2020, View Source [SID1234553088]).

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On January 13, 2020 Pear Therapeutics, Inc. the leader in Prescription Digital Therapeutics (PDTs), reported that it has entered into an agreement with Apricity Health, LLC to develop up to two product candidates for precision management of patients undergoing cancer treatment (Press release, Pear Therapeutics, JAN 13, 2020, View Source [SID1234553104]). Apricity, a pioneer in leveraging technology and analytics to address the expertise gap in real-world medicine, is developing its first product candidate, ApricityRx, to enable intelligent monitoring and precision management of patients receiving immune checkpoint therapies. As part of the agreement, Pear will have the option to license two oncology PDTs arising out of this combined effort.

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IO is transforming cancer care, but there remains a major unmet need in maximizing its real-world effectiveness and minimizing associated toxicities. Founded by world renowned physician scientists in cancer and immuno-oncology, with an august advisory board of clinical experts led by Nobel Laureate Dr. James Allison, Apricity’s mission is to deliver clinical expertise with digital technology at the point of care to help practicing oncologists and nurses better manage IO-related toxicities in patients receiving IO therapies.

"Dr. Allison, an inventor of immune checkpoint therapy, has shown us that targeting the immune system can potentially cure cancer patients. Our team of expert advisors has over a decade of experience treating patients on IO therapies and managing their toxicities to help them stay on treatment with better outcomes," said Lynda Chin, M.D., President and CEO of Apricity Health. "We now need to share our expertise with real world practitioners so more patients can benefit from these revolutionary new medicines. We believe our synergistic collaboration with Pear will help us get there faster."

"By combining Pear’s platform and infrastructure with Apricity’s clinical expertise and analytics, we believe we can enhance the effectiveness of cancer treatment for patients," said Corey McCann, M.D., Ph.D., President and CEO of Pear Therapeutics. "PDTs like ApricityRx may have the potential to directly improve efficacy when prescribed in combination with IO medications."

On January 13, 2020 Genome & Company (KONEX: 314130) is reported that it has entered into a clinical trial collaboration and supply agreement with Merck KGaA, Darmstadt, Germany and Pfizer Inc. to evaluate the safety, tolerability, biological and clinical activities of GEN-001 therapy in combination with avelumab, a human anti-PD-L1 therapy, in multiple cancer indications (Press release, Genome & Company, JAN 13, 2020, View Source;company-announces-a-clinical-trial-collaboration-and-supply-agreement-with-merck-kgaa-darmstadt-germany-and-pfizer-300985435.html [SID1234553121]).

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Under the terms of this agreement, Genome & Company will be the sponsor of the study, and Merck KGaA, Darmstadt, Germany and Pfizer will supply avelumab for the phase 1/1b clinical trial that is expected to be commenced in 2020 in the U.S. Both parties will have access to the clinical data.

The combination trial is designed to be a first-in-human (FIH) study including dose escalation and expansion cohorts to evaluate the safety and preliminary efficacy.

"GEN-001 has been developed as the backbone of Genome & Company’s immuno-oncology pipeline, and we are delighted to collaborate with the global leaders in oncology such as Merck KGaA, Darmstadt, Germany and Pfizer on this phase 1/1b clinical trial for this combination of GEN-001 and avelumab. We are excited to investigate how the preclinical data of this combination will be translated to humans. We look forward to initiating this clinical trial in the coming months," said Dr. Jisoo Pae, CEO of Genome & Company.

Avelumab Approved Indications

Avelumab (BAVENCIO) in combination with axitinib is indicated in the US for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

The US Food and Drug Administration (FDA) also granted accelerated approval for avelumab (BAVENCIO) for the treatment of (i) adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (mMCC) and (ii) patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy, or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. These indications are approved under accelerated approval based on tumor response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.

Avelumab is currently approved for patients with in 50 countries globally, with the majority of these approvals in a broad indication that is not limited to a specific line of treatment.

Avelumab Important Safety Information from the US FDA-Approved Label

The warnings and precautions for avelumab (BAVENCIO) include immune-mediated adverse reactions (such as pneumonitis and hepatitis [including fatal cases], colitis, endocrinopathies, nephritis and renal dysfunction and other adverse reactions [which can be severe and have included fatal cases]), infusion-related reactions, hepatotoxicity, major adverse cardiovascular events (MACE) [which can be severe and have included fatal cases], and embryo-fetal toxicity.

Common adverse reactions (reported in at least 20% of patients) in patients treated with BAVENCIO monotherapy include fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction, peripheral edema, decreased appetite/hypophagia, urinary tract infection and rash. Common adverse reactions (reported in at least 20% of patients) in patients receiving BAVENCIO in combination with axitinib include diarrhea, fatigue, hypertension, musculoskeletal pain, nausea, mucositis, palmar-plantar erythrodysesthesia, dysphonia, decreased appetite, hypothyroidism, rash, hepatotoxicity, cough, dyspnea, abdominal pain and headache. Grade 3-4 clinical chemistry and hematology laboratory value abnormalities reported in at least 10% of patients treated with BAVENCIO monotherapy include hyponatremia, lymphopenia, GGT increased; in patients receiving BAVENCIO in combination with axitinib, grade 3-4 clinical chemistry and hematology laboratory value abnormalities included blood triglyceride increased and lipase increased.

For full Prescribing Information and Medication Guide for BAVENCIO, please see www.BAVENCIO.com.

About GEN-001

GEN-001 is an oral microbiome therapeutic candidate developed to have immune modulating activities, resulting in potential partnership with immune checkpoint inhibitors. GEN-001 consists a single strain bacteria isolated from gut of healthy human volunteers that has been shown to activate dendritic cells, macrophages and T cell response. In preclinical studies, GEN-001 has shown optimal safety margin and synergistic effects in combination with immune checkpoint inhibitors by enhancing the effect of suppressing the growth of both immune checkpoint inhibitor sensitive and resistant tumor models.

On January 13, 2020, Monopar Therapeutics Inc ("Monopar" or the "Company") reported that it has entered into a Capital on DemandTM Sales Agreement (the "Agreement") with JonesTrading Institutional Services LLC, as sales agent ("JonesTrading" or the "Agent"), pursuant to which Monopar may offer and sell, from time to time, through or to JonesTrading shares of Common Stock, par value $0.001 per share, of Monopar having an aggregate offering price of up to $19.7 million (the "Shares") (Filing, 8-K, Monopar Therapeutics, JAN 13, 2020, View Source [SID1234553142]).

The offer and sale of the Shares will be made pursuant to a shelf registration statement on Form S-3 and the related prospectus (File No. 333-235791) filed by the Company with the Securities and Exchange Commission (the "SEC") on January 3, 2020 and declared effective by the SEC on January 13, 2020, as supplemented by a prospectus supplement dated January 13, 2020 and filed with the SEC pursuant to Rule 424(b) under the Securities Act of 1933, as amended (the "Securities Act"). This Current Report on Form 8-K shall not constitute an offer to sell or the solicitation of an offer to buy the Company’s Common Stock discussed herein, nor shall there be any offer, solicitation, or sale of the Company’s Common Stock in any state in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state.

Monopar is not obligated to sell any Shares under the Agreement.

Upon delivery of a placement notice by Monopar and subject to the terms and conditions of the Agreement and such placement notice, JonesTrading may sell the Shares by methods deemed to be an "at the market offering" as defined in Rule 415(a)(4) promulgated under the Securities Act and will use commercially reasonable efforts consistent with its normal trading and sales practices and applicable state and federal law, rules and regulations and the rules of Nasdaq Capital Market, to sell the Shares from time to time.

The offering of Shares pursuant to the Agreement will terminate upon the earlier of (a) the sale of all of the Shares subject to the Sales Agreement or (b) the termination of the Sales Agreement by JonesTrading or the Company, as permitted therein.

The Company has agreed to pay JonesTrading commissions for its services in acting as agent in the sale of the Shares in the amount of up to 3.0% of gross proceeds from the sale of the Shares pursuant to the Agreement. The Company has also agreed to provide JonesTrading with customary indemnification and contribution rights, in connection with entering into the Agreement.

The foregoing description of the Agreement is not complete and is qualified in its entirety by reference to the full text of such agreement, a copy of which is filed herewith as Exhibit 1.1 to this Current Report on Form 8-K and is incorporated herein by reference.

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