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Cancer vaccine firm Oxford Vacmedix announces Innovate UK grant for novel application of ROP technology

On December 19, 2019 Oxford Vacmedix UK Limited (OVM), the UK-based biopharma company focusing on the development of cancer vaccines, reported the award of an Innovate UK grant to fund research that capitalises on OVM’s proprietary recombinant overlapping peptide (ROP) technology (Press release, Oxford Vacmedix, DEC 19, 2019, View Source [SID1234553210]). The research will be carried out in collaboration with Imperial College in London and the Ditan hospital in Beijing, the leading infectious disease hospital in China. The project aims to develop a low-cost diagnostic test to detect bacteria resistant to carbapenem antibiotics. This will have advantages in terms of speed, simplicity and cost over DNA sequencing approaches, and will be accessible for low and middle income countries. These prototype assays will be produced at OVM and Imperial College and will be trialled at the Ditan Hospital. Patients in intensive care are at high risk of bacterial infections, a significant proportion of which are resistant to front-line antibiotics.

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The need to monitor and control resistance to antimicrobial therapy has been identified as an urgent global priority by both the WHO and UN. The rise in carbapenem resistance is of particular concern given the importance of this class of antibiotics in the intensive care setting, and its role as a marker for multiple antibiotic drug resistance. The availability of an inexpensive and simple test for carbapenem resistance will enable early identification of affected patients in the community. Once identified, patients can be isolated, appropriate treatment started earlier and clinical control measures put in place.

Spun out from the University of Oxford, OVM is commercialising the research on ROPs developed in the Department of Oncology at the University of Oxford. The principal application of the technology is in the development of a novel type of therapeutic cancer vaccine with potential for increased efficacy, simpler regulatory pathways and lower costs.

This new diagnostic project will run alongside OVM’s main development programmes and will be largely outsourced, allowing the company to focus on the development of its two lead cancer vaccines; OVM-100, an HPV vaccine targeted at cervical cancer; and OVM-200 a new type of vaccine based on survivin that targets solid tumours. Both vaccines address areas of significant unmet medical need and will be tested as single agents and also in combination with other immune-oncology (IO) agents.

Dr Shisong Jiang, CSO and Founder of OVM, said:

"We are very pleased to have this opportunity to work with Imperial College and with the Ditan hospital in Beijing on this important project. This novel application of our recombinant overlapping peptide technology could show real utility in the diagnosis and management of carbapenem resistance and could make a significant difference to the effectiveness of treatment for infectious disease. We very much appreciate the support and funding from Innovate UK for this project"

Professor Xu Xiao-Ning, Chair of Human Immunology at the Imperial College London added:

"This project is an excellent opportunity to widen the applications of the Oxford Vacmedix’s ROP technology and to build on the expertise in immunology and infectious disease at Imperial College. We look forward to a successful collaboration and to developing early diagnosis of carbapenem resistance, to address this real need and benefit a wide population with sometimes limited access to healthcare".

MacroGenics Announces Submission of Margetuximab Biologics License Application to U.S. FDA

On December 19, 2019 MacroGenics, Inc. (Nasdaq: MGNX), a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, reported that the Company has submitted a Biologics License Application (BLA) for margetuximab, an investigational, Fc-engineered, monoclonal antibody that targets HER2 (Press release, MacroGenics, DEC 19, 2019, View Source [SID1234553174]). The margetuximab BLA is for the treatment of patients with metastatic HER2-positive breast cancer in combination with chemotherapy. The submission is based on the safety and efficacy results of the pivotal phase 3 SOPHIA study, which were first presented at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting, with updated data recently presented at the 2019 San Antonio Breast Cancer Symposium.

"As the Company’s first BLA submission, this is a key milestone for MacroGenics. We are grateful to the patients who participated in this study, as well as their families, and all involved in developing margetuximab," said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. "With this submission, we look forward to working with the Agency to bring margetuximab to appropriate patients. We believe the positive clinical trial results in SOPHIA demonstrate margetuximab’s potential as a treatment option for patients living with this devastating disease."

About the SOPHIA Study

The SOPHIA study (NCT02492711) is a randomized, open-label Phase 3 clinical trial evaluating margetuximab plus chemotherapy compared to trastuzumab plus chemotherapy in patients with HER2-positive metastatic breast cancer, who have previously been treated with anti-HER2-targeted therapies. All study patients had previously received trastuzumab and pertuzumab, and approximately 90% had previously received ado-trastuzumab emtansine, or T-DM1.

The study enrolled 536 patients who were randomized 1:1 to receive either margetuximab (n=266) given intravenously at 15 mg/kg every three weeks or trastuzumab (n=270) given intravenously at 6 mg/kg (or 8 mg/kg for loading dose) every three weeks in combination with one of four chemotherapy agents (capecitabine, eribulin, gemcitabine or vinorelbine) given at the standard dose. Intent-to-treat PFS analysis occurred after 265 PFS events, and the first and second interim OS analyses occurred after 158 and 270 OS events, respectively. Final OS analysis is planned after 385 events and is expected to occur in the second half of 2020.

Primary endpoints are sequentially-assessed PFS, determined by centrally-blinded radiological review, and OS. Key secondary endpoints are PFS by investigator assessment and ORR. Tertiary endpoints include ORR by investigator assessment and safety. PFS and ORR were assessed according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Effect of CD16A (FcγRIIIa) 158 genotype on margetuximab activity is a pre-specified exploratory endpoint.

About Margetuximab

Margetuximab is an investigational monoclonal antibody that targets the HER2 oncoprotein. Margetuximab was designed to provide HER2 blockade and has similar HER2 binding and antiproliferative effects as trastuzumab. In addition, the Fc region of margetuximab has been engineered to enhance the engagement of the immune system. Margetuximab is also being evaluated in combination with anti-PD-1 therapy for the potential treatment of patients with HER2-positive gastric or gastroesophageal junction cancer. MacroGenics has initiated the Phase 2/3 MAHOGANY study (NCT04082364). For more information, please visit www.clinicaltrials.gov.

Onconova Therapeutics, Inc. Announces Closing Of $5.0 Million Registered Direct Offering Priced At-The-Market

On December 20, 2019 Onconova Therapeutics, Inc. (NASDAQ: ONTX) ("Onconova" or the "Company"), a Phase 3-stage biopharmaceutical company discovering and developing novel products to treat cancer, with an initial focus on myelodysplastic syndromes (MDS), reported the closing of its previously announced registered direct offering of 13,878,864 shares of its common stock and warrants to purchase up to 6,939,432 shares of its common stock, at a combined purchase price of $0.36026 per share and associated warrant, for aggregate gross proceeds of approximately $5.0 million (Press release, Onconova, DEC 19, 2019, View Source [SID1234552558]). The registered direct offering priced at-the-market under Nasdaq rules.

H.C. Wainwright & Co. acted as the exclusive placement agent for the offering.

The warrants issued in the offering have an exercise price of $0.298 per share and exercise period commencing immediately upon issuance and a term of five (5) years.

The Company intends to use the net proceeds from the offering for working capital and general corporate purposes, including advancing preparations for a planned New Drug Application (NDA) filing to the FDA for intravenous rigosertib in second-line higher-risk MDS in 2020. The Company surpassed 90% of the required enrollment of the INSPIRE Trial in November 2019 and anticipates reporting topline data in the first half of 2020, following full enrollment and reaching the number of required survival events. With the additional proceeds from the offering, the Company believes that it has the sufficient funds to extend operations and ongoing trials late into the fourth quarter of 2020.

Onconova was notified December 18, 2019, that The Nasdaq Stock Market LLC ("Nasdaq") staff has determined that the Company has cured the previously reported stockholder’s equity deficiency and regained compliance with the Nasdaq stockholders’ equity requirement for continued listing on The Nasdaq Capital Market, based upon the Company’s recent financing transactions. Accordingly, the previously announced Nasdaq Hearings Panel scheduled for December 19, 2019 has been cancelled.

The securities described above were offered and sold by the Company pursuant to a "shelf" registration statement on Form S-3 (Registration No. 333-221684), including a base prospectus, previously filed with and declared effective by the Securities and Exchange Commission (the "SEC") on December 28, 2017. The offering of the securities was made only by means of a prospectus supplement that forms a part of the registration statement. A final prospectus supplement and an accompanying base prospectus relating to the registered direct offering was filed with the SEC and is available on the SEC’s website located at View Source Electronic copies of the prospectus supplement and the accompanying base prospectus may also be obtained by contacting H.C. Wainwright & Co., LLC at 430 Park Avenue, 3rd Floor, New York, NY 10022, by phone at 646-975-6996 or e-mail at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

Entry into a Material Definitive Agreement

On December 19, 2019, Heron Therapeutics, Inc. (the "Company") reported that it entered into a Third Amendment to Lease (the "Lease Amendment") with ARE-SD REGION NO. 61, LLC, successor-in-interest to AP3-SD1 Campus Point LLC (the "Landlord"), amending that certain Lease, dated October 18, 2016, as amended by that certain First Amendment to Lease, dated March 15, 2017, and further amended by that certain Second Amendment to Lease, dated May 8, 2018, all by and between the Company and the Landlord (the "Lease") (Filing, 8-K, Heron Therapeutics, DEC 19, 2019, View Source [SID1234552554]). The Lease Amendment provides for the Company to lease additional office space in the building located at 4242 Campus Point Court, San Diego, California, for a period of approximately 72 months, commencing on or about January 1, 2020. Pursuant to the Lease Amendment, the Company has agreed to pay a basic annual rent for the additional office space that increases incrementally over the term of the Lease Amendment from approximately $0.9 million for the first 12 months of the Lease Amendment (inclusive of certain rent abatements) to approximately $1.3 million for the last 12 months of the Lease Amendment, and such other amounts as set forth in the Lease Amendment. The Company also paid to the Landlord an additional security deposit in an amount less than $0.1 million. Except as modified by the Lease Amendment, all of the provisions of the Lease will continue unmodified and in full force and effect.

The foregoing description of the terms of the Lease Amendment does not purport to be complete and is qualified in its entirety by reference to the full text of the Lease Amendment, a copy of which is filed herewith as Exhibit 10.1 to this Current Report on Form 8-K.

INSIGHT-004 CLINICAL TRIAL UPDATE

On December 19, 2019 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a biotechnology company developing novel immunotherapy treatments for cancer and autoimmune diseases, reported an update on the INSIGHT-004 Phase I clinical trial to evaluate the combination of eftilagimod alpha ("efti" or "IMP321") with avelumab, a human anti-PD-L1 antibody, in patients with advanced solid malignancies (Press release, Immutep, DEC 19, 2019, View Source [SID1234552545]).

Following full recruitment of the first cohort of 6 patients receiving avelumab (standard dose) and efti (6 mg), Immutep’s partner IKF has now commenced the recruitment of patients into the second cohort (standard dose avelumab, with 30 mg efti) which will involve also 6 participants.

No new safety signals or dose limiting toxicities have been reported from the first cohort of patients. The observed safety profile also aligns with the known safety profile of the monotherapies.

Participants enrolled in this trial are patients with late-stage cancer who have been heavily pre-treated for advanced, metastatic solid tumors. Typically, they have no other therapy options available. Out of 6 patients, 1 patient experienced a partial response according to RECIST 1.1.

More data from the study is expected to be reported in H1 CY2020.

Prof. Dr. Salah-Eddin Al-Batran, lead investigator of INSIGHT-004 commented: "We are really pleased that INSIGHT-004 recruitment is advancing and that we can start to enroll the second cohort of 6 patients. The treatment’s safety profile is consistent with previous trials of efti which is encouraging and it’s also good to see early activity signals with one patient reporting a partial response already."

INSIGHT-004 is the fourth arm of the INSIGHT trial which is being conducted by Institute of Clinical Cancer Research, Krankenhaus Nordwest GmbH in Frankfurt, Germany (IKF). It is being conducted under Immutep’s collaboration with Merck KGaA, Darmstadt, Germany and Pfizer Inc and is evaluating the safety, tolerability and recommended Phase II dose of Immutep’s lead immunotherapy product candidate efti when given in combination with avelumab in 12 patients with advanced solid malignancies.

Immutep Ltd, Level 12, 95 Pitt Street, Sydney NSW 2000

Phone: +61 2 8315 7003 Fax: +61 2 8569 1880

www.immutep.com ABN: 90 009 237 889

About INSIGHT-004

INSIGHT-004 is being conducted as an amendment to the ongoing INSIGHT Phase I clinical trial. The Institute of Clinical Cancer Research, Krankenhaus Nordwest GmbH in Frankfurt, Germany ("IKF") is the sponsor of the clinical trial which is being conducted under the existing protocol of the ongoing INSIGHT clinical study. Prof. Dr. Salah-Eddin Al-Batran, the lead investigator of INSIGHT and member of Immutep’s clinical advisory board, is the lead investigator of INSIGHT-004.

For more information regarding INSIGHT-004 which forms part of the INSIGHT trial, visit clinicaltrials.gov (INSIGHT identifier NCT03252938). INSIGHT-004 refers to the fourth arm of the INSIGHT trial where IMP321 is given in combination with avelumab.

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 MCC 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,

Immutep Ltd, Level 12, 95 Pitt Street, Sydney NSW 2000

Phone: +61 2 8315 7003 Fax: +61 2 8569 1880

www.immutep.com ABN: 90 009 237 889

dysphonia, decreased appetite, hypothyroidism, rash, hepatotoxicity, cough, dyspnea, abdominal pain and headache. Clinical chemistry and hematology laboratory value abnormalities reported in at least 10% of patients include hyponatremia, lymphopenia, GGT increased, blood triglyceride increased and lipase increased, and grade 3-4 lymphopenia, anemia, elevated cholesterol and liver enzymes.