On November 16, 2020 Trillium Therapeutics Inc. ("Trillium" or the "Company") (NASDAQ/TSX: TRIL), a clinical stage immuno-oncology company developing innovative therapies for the treatment of cancer, reported financial and operating results for the nine months ended September 30, 2020 (Press release, Trillium Therapeutics, NOV 16, 2020, View Source [SID1234571146]).

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"Third quarter was a productive quarter for Trillium," said Jan Skvarka, the Company’s President and Chief Executive Officer. "We reported encouraging clinical data updates for both TTI-622 and TTI-621, announced a $25 million equity investment from Pfizer, raised $150 million in a follow-on offering, and added Dr. Michael Kamarck to the Board of Directors. After the close of the third quarter, we announced formation of a Scientific Advisory Board, appointment of Dr. Ingmar Bruns as our new Chief Medical Officer, and addition of Mr. Paolo Pucci to the Board of Directors. With close to $300 million in cash, we are well capitalized to embark on a Phase 2 program in heme and solid tumor malignancies in 2021."

TTI-622 Study Update provided in the third quarter of 2020:

In the Phase 1a/1b study in patients with advanced relapsed or refractory lymphoma or multiple myeloma (NCT03530683), the Company reported that a total of six objective responses (33%; 1 complete response, 5 partial responses) have been observed among 18 response evaluable patients treated at dose levels of 0.8, 2.0, 4.0 and 8.0 mg/kg. Responses had occurred across all dose levels in this range, with three of six (50%) patients achieving responses in the 8.0 mg/kg cohort (response assessment for one additional patient at 8 mg/kg dose not available as of the cutoff date).
The safety assessment of the 8 mg/kg dosing cohort was successfully completed with one Grade 4 thrombocytopenia dose-limiting toxicity (DLT) reported among the six evaluable patients and no additional Grade 3 or higher thrombocytopenia events observed.
Clinical responses had been observed across multiple lymphoma indications, including diffuse large B-cell lymphoma, cutaneous T-cell lymphoma with large cell transformation, peripheral T-cell lymphoma, and follicular lymphoma.
All responses were observed at the first assessment at 8 weeks.
The study began enrolling patients at the 12 mg/kg dose level.
TTI-621 Study Update provided in the third quarter of 2020:

In the Phase 1 study in patients with advanced relapsed or refractory hematologic malignancies (NCT02663518), preliminary data from Part 4 indicated the weekly infusions of TTI-621 up to 1.4 mg/kg were well tolerated without dose-limiting thrombocytopenia. Platelet decreases generally occurred on dosing days, recovered in 2-4 days, and had not worsened with increasing dose levels. Infusion-related reactions (IRRs) typically occurred during initial infusions and often resolved without recurrence. One Grade 3 IRR DLT was observed at 1.0 mg/kg.
Antitumor activity in the 1 mg/kg cohort included 1 partial response and 1 skin complete response (overall assessment stable disease) in 6 evaluable patients; 2 patients were bridged to allogeneic transplantation. Preliminary data suggested dose-dependent improvements in modified severity weighted assessment tool (mSWAT) scores in the 0.5 to1.0 mg/kg cohorts (1.4 mg/kg cohort data not yet available).
The study began enrolling patients at the 2.0 mg/kg dose level.
Financings:
In September 2020, the Company issued 2,297,794 common shares at a price of $10.88 per share to Pfizer Inc. in a registered direct offering. The gross proceeds from this offering were $25.0 million, before deducting offering expenses of $0.1 million.

In September 2020, the Company also completed an underwritten public offering of 11,500,000 common shares, at a public offering price of $13.00 per share. The number of shares sold include 1,500,000 common shares pursuant to the full exercise by the underwriters of their option to purchase additional common shares. The gross proceeds from this offering were $149.5 million, before deducting underwriting discounts and commissions, and offering expenses of $9.1 million.

Governance changes:
In September 2020, Dr. Michael Kamarck joined the Board of Directors. Dr. Kamarck is Chief Technology Officer for Vir Biotechnology, Inc. and has significant experience and expertise with the development and manufacturing of biologic products.

In addition, Paolo Pucci joined the Board of Directors on November 12, 2020 and brings significant expertise in oncology drug development and commercialization. He most recently served as CEO of ArQule until it was acquired by Merck for $2.7 billion in January 2020.

Third Quarter 2020 Financial Results:
As of September 30, 2020, Trillium had cash and cash equivalents and marketable securities of $292.4 million, compared to $22.7 million at December 31, 2019. The increase in cash and cash equivalents and marketable securities was due mainly to proceeds from financings completed in January 2020 and September 2020.

Net loss for the nine months ended September 30, 2020 of $173.0 million was higher than the loss of $22.4 million for the nine months ended September 30, 2019. The net loss was higher due mainly to a net warrant liability revaluation loss of $132.7 million, a loss of $22.1 million on the revaluation of the deferred share unit (DSU) liability (reclassified from a liability to equity effective June 30, 2020 on adoption of the new omnibus incentive plan), and higher manufacturing costs. This was partially offset by lower clinical trial expenses, salary expenses, intangible assets amortization, and share-based compensation. Trillium’s outstanding warrants are a non-cash liability, and revaluation losses on the Company’s warrant liability balance are of a non-cash nature.

On November 16, 2020 Mateon Therapeutics, Inc. ("Mateon" or the "Company") (OTCQB: MATN) reported financial results for the third quarter ended September 30, 2020 ("Q3 2020"), as well as an update on its therapeutic development initiatives, including those related to COVID-19 (Press release, Mateon Therapeutics, NOV 16, 2020, View Source [SID1234571145]).

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Recent Operational Highlights

●ArtiShield (outside of India)/ARTIVeda (India)

oSigned an agreement with Windlas Biotech Pvt. Ltd. of India to commercialize ArtiShield /ARTIVeda, the Company’s lead ethnobiology dru,g designed to be a readily available and cost-effective agent to combat COVID-19;
oArtiShield /ARTIVeda approved for manufacture and marketing by the Ministry of AYUSH (Ayurveda, Yoga and Naturopathy, Unani, Siddha and Homoeopathy), license number UK.AY-401/2018, for the treatment of various symptoms like fever and inflammation frequently seen in COVID-19 patients;
oDr. Suhas Kshirsagar, B.A.M.S, M.D. (Ayurveda), a worldwide renowned ayurvedic expert, joined Mateon as an advisor for Mateon’s Ayurvedic product ARTIShield /ARTIVeda in its commercialization for COVID-19;
oDr. Suhas Kshirsagar led a successful symposium entitled: "Advancing Ayurveda Through Ethnobiology Drug Development." Topics included Mateon’s ARTIShield/ ARTIVeda for the Treatment of COVID-19 and COVID-19/Influenza Coinfection. Presentations can be viewed at View Source;feature=youtu.be.
oCommenced patient enrollment for its ARTI-19 Phase IV multi-center interventional study to evaluate the safety and efficacy of ArtiShield in the treatment of adults with COVID-19 in India. This global study will evaluate the safety and efficacy of ArtiShield upto 3,000 total patients, 120 of whom are currently from India and further expandable to 300 patients from India. Top line data from ARTI-19 in India is expected between Q4 2020 and Q1 2021;

●OT-101/COVID-19 program
oReceived clearance from regulatory authorities in Argentina and Peru to initiate a Phase II clinical trial of OT-101, a TGF-β antisense, for the treatment of patients with mild to severe COVID-19 infection. Top line data from the study is currently expected during or before Q1 2021. If the outcome is positive, the data will form the basis for Emergency Use Approval (EUA) application to global regulatory bodies. Including the US Food and Drug Administration (FDA);

oContinuing our partnership with Golden Mountain Partners (GMP) and/or their designee with drawdown of the $2.0 M debt financial instrument with GMP to conduct OT-101/COVID-19 clinical trial.

●Oxi4503/ Melanoma

oAnnounced that the US FDA granted Rare Pediatric Disease (RPD) designation to OXi4503 (combretastatin A1-diphosphate; CA1P) for the treatment of acute myeloid leukemia due to genetic mutations that disproportionately affect pediatric patients. The FDA grants RPD designation for diseases with serious or life-threatening manifestations that primarily affect people aged from birth to 18 years, and that affect fewer than 200,000 people in the U.S.; and

●Strengthened our scientific and management teams with the appointments of Anthony Maida, III, Ph.D., MA, MBA as Chief Clinical Officer – Translational Medicine to drive the Company’s clinical development activity.
"We are very encouraged by the progress being made at Mateon through the first nine months of 2020," said Dr. Vuong Trieu, CEO of Mateon. "While our product portfolio addresses significant unmet needs with respect multiple disease states, including glioblastoma, melanoma, and pancreatic cancer, we are most excited by our strategy to focus on COVID-19 and COVID-19/influenza coinfection. We look forward to multiple clinical trial catalysts – notably top line data from our ARTI-19 Phase IV trial between Q4 2020 and Q2 2021 the end of this year – and are excited about the transformational opportunities that our therapies may provide."

"We are excited about the commercialization of ARTIVeda in India. It is expected to be a cost-effective treatment and prophylactic for COVID-19. This is transformational for the Company, as we establish a consortium of manufacturers, distributors, and marketers for the equitable distribution of this COVID-19 therapy," said Amit Shah, CFO of Mateon.

On November 16, 2020 Istari Oncology, Inc., a clinical-stage biotechnology company, reported that the U.S. Food and Drug Administration (FDA) has accepted the Investigational New Drug application (IND) for a Phase 2 clinical trial, LUMINOS-102, to investigate the efficacy and safety of PVSRIPO alone or in combination with a programmed death receptor-1 (anti-PD-1) inhibitor in patients with treatment-refractory melanoma (Press release, Istari Oncology, NOV 16, 2020, View Source [SID1234571144]).

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PVSRIPO is a novel viral immunotherapy that activates a patient’s innate and adaptive immunity to facilitate a targeted anti-tumor immune response. Following positive Phase 1 results in patients with unresectable and/or metastatic melanoma, the new IND will enable continued development of PVSRIPO for advanced melanoma. LUMINOS-102 (NCT04577807) will assess PVSRIPO’s impact on patients who have failed anti-PD-1 therapy.

"There is a massive need for treatments targeted at patients who experience primary or acquired resistance to anti-PD-1 therapies," said W. Garrett Nichols, MD, MS, Chief Medical Officer at Istari Oncology. "PVSRIPO has shown promise in treating patients that have failed primary treatment options across multiple solid tumor types. We look forward to building on the positive results of our initial Phase 1 trial in melanoma with LUMINOS-102."

Following a safety run-in, approximately 50 participants with cutaneous or mucosal melanoma who previously failed anti-PD-1 blockade will be randomized 1:1 to receive either PVSRIPO or PVSRIPO plus an anti-PD-1.

Site initiation activities are underway for this Phase 2 trial, which the Company anticipates will begin in the first quarter of 2021. An interim analysis is planned once 20 patients have been randomized and treated for 3 months. Patient outcomes, including objective response rates (by RESICST criteria), durability of responses, and overall survival will be measured over a 24-month time frame.

In a Phase 1 study of PVSRIPO monotherapy in anti-PD1 refractory advanced melanoma presented by Dr. Georgia Beasley and colleagues at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2020 Annual Meeting last week, the overall response rate in subjects who received three single intralesional injections three weeks apart (maximum number administered in the study) was 67% (4/6), suggesting that PVSRIPO was able to initiate or rekindle responses in patients who have failed anti-PD-1 therapy. Responses were observed in both injected and uninjected tumors (e.g. an abscopal response). No serious adverse events or dose limiting toxicities were observed.

For more information about Istari Oncology and their ongoing clinical trials, visit istarioncology.com.

About PVSRIPO
PVSRIPO is a virus based on the live attenuated Sabin type 1 polio vaccine that has been genetically modified for safety. Unlike other viral immunotherapies, PVSRIPO has a distinct target (the poliovirus receptor CD155), which is widely expressed in neoplastic cells of most solid tumors. Via CD155, PVSRIPO targets tumors with two primary mechanisms: 1) direct damage to and killing of cancerous cells; and 2) engaging innate and adaptive antitumor immune responses via sublethal infection of antigen presenting cells in the tumor, which unleash an inflammatory cascade resulting in sustained systemic antitumor immunity. PVSRIPO has been granted Breakthrough Therapy Designation and Orphan Status by the FDA in recurrent glioblastoma.

About Melanoma
There are estimated to be over 12,000 new and recurrent cases of advanced, unresectable melanoma diagnosed in the U.S. each year, and around 7,000 deaths. While immune checkpoint inhibitors have dramatically improved the outlook for advanced melanoma patients today, most patients treated with these immunotherapies are either primary non-responders or eventually develop immune-refractory progressive disease and require additional therapy.

On November 16, 2020 Molecular Templates, Inc. (Nasdaq: MTEM, "Molecular Templates" or "MTEM"), a clinical-stage biopharmaceutical company focused on the discovery and development of the company’s proprietary engineered toxin bodies (ETBs), which are differentiated, targeted, biologic therapeutics for cancer and other serious diseases, reported that it will deliver presentations and participate in 1on1 meetings at the Stifel 2020 Virtual Healthcare Conference and the 3rd Annual Evercore ISI HealthCONx Conference (Press release, Molecular Templates, NOV 16, 2020, View Source [SID1234571142]). In addition, management will be available for virtual 1on1 meetings at the Jefferies Virtual London Healthcare Conference.

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Stifel 2020 Virtual Healthcare Conference
Conference Dates: November 16-18
Presentation Date and Time: November 17 at 9:20am ET

Jefferies Virtual London Healthcare Conference
Conference Dates: November 17 – 19
Available for 1on1 meetings

3rd Annual Evercore ISI HealthCONx Conference
Conference Dates: December 1-3
Presentation Date and Time: December 3 at 10:05am ET
Live webcasts of the Stifel and Evercore ISI presentations will be available in the "News and Events" section of the MTEM website at www.mtem.com. Additionally, replays of the webcasts will be available on the corporate website following the conferences.

On November 16, 2020 Zymeworks Inc. (NYSE: ZYME), a clinical-stage biopharmaceutical company developing multifunctional biotherapeutics, and ALX Oncology Holdings Inc. (NASDAQ: ALXO), a clinical-stage immuno-oncology company developing therapies that block the CD47 checkpoint pathway, reported they have entered into a clinical collaboration to evaluate the combination of Zymeworks’ zanidatamab (formerly ZW25), a HER2-targeted bispecific antibody, and ALX148, a next-generation CD47 blocker, for the treatment of patients with advanced HER2-expressing breast cancer and other solid tumors (Press release, Zymeworks, NOV 16, 2020, View Source [SID1234571141]).

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Under the terms of the agreement, Zymeworks will conduct an open label, multi-center Phase 1b study to assess the safety and efficacy of the combination of zanidatamab and ALX148 in a two-part study. The first part of the trial will evaluate the safety of the combination treatment. The second part of the trial will evaluate the safety, tolerability and anti-tumor activity of the combination in separate cohorts of subjects with HER2-positive breast cancer, HER2-low breast cancer, and non-breast HER2-expressing solid tumors.

"In addition to broad anti-tumor activity, zanidatamab’s safety profile supports combination approaches with other therapeutics," said Diana Hausman, M.D., Chief Medical Officer at Zymeworks. "Our collaboration with ALX Oncology and their CD47 blocker, ALX148, has the potential to further expand the opportunity for zanidatamab to provide benefit to a broader population of patients, including those with advanced HER2-expressing breast cancer."

Zanidatamab is designed to have multiple mechanisms of action, including immune clearance of HER2-expressing tumor cells by macrophages through antibody-dependent cellular phagocytosis (ADCP). CD47 is a "don’t eat me" signal that acts as a checkpoint inhibitor to macrophages. Cancer cells that express CD47 are resistant to immune clearance even when targeted with therapeutic antibodies. Treatment with zanidatamab plus ALX148 has the potential to increase the immune clearance of HER2-expressing cancer cells by combining a biparatopic antibody capable of binding at higher density than monospecific antibodies with a molecule that blocks CD47 on the same targeted cancer cells.

"We are excited about this collaboration with Zymeworks that combines two promising next-generation anti-cancer agents, a HER2-targeted bispecific antibody with a CD47 blocker, to enhance their potential activity in treating patients with advanced breast cancer," said Jaume Pons, Ph.D., Founder, President and Chief Executive Officer of ALX Oncology. "ALX148 was designed for safe use in combination to maximize clinical activity with a range of anti-cancer agents. This collaboration builds on the promising anti-tumor activity observed in clinical trials of ALX148 combined with a HER2-targeted therapy in patients with advanced HER2-positive gastric and gastroesophageal cancer."

Zanidatamab is in advanced clinical development, actively enrolling a pivotal study in patients with previously-treated HER2 gene-amplified biliary tract cancer. In addition, five active Phase 2 programs are underway, and Zymeworks plans to initiate a second pivotal study for zanidatamab as first-line treatment for advanced HER2-positive gastroesophageal adenocarcinomas.

Phase 1 studies of ALX148 have been conducted in combination with tumor antigen targeted antibodies, a checkpoint inhibitor and chemotherapy. Preliminary results from ASPEN-01, the ALX148 Phase 1b study, were presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s 35th Anniversary Annual Meeting [abstract 404]. ALX148 displayed promising initial clinical activity in patients with solid tumors, including advanced HER2-positive gastric and gastroesophageal cancer where ALX148 was well tolerated in combination with an anti-HER2 specific antibody and chemotherapy with no maximum tolerated dose reached. ALX Oncology plans to continue the advancement of ALX148 as a potential treatment for a range of solid tumor indications and is currently also in development in patients with higher risk myelodysplastic syndromes (ASPEN-02).