On March 24, 2022 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC) reported that its partner Adlai Nortye has advanced to the third and final dose escalation cohort of the bridging clinical trial evaluating the safety, tolerability, and preliminary efficacy of pelareorep-paclitaxel combination therapy in Chinese patients with advanced or metastatic breast cancer (Press release, Oncolytics Biotech, MAR 24, 2022, View Source [SID1234610881]). The trial’s first two cohorts have completed their dose escalation evaluation periods and indicated pelareorep in combination with paclitaxel was well-tolerated with no new safety signals observed to date.

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The dosing regimens for the bridging trial’s second and third cohorts are equivalent to those administered in Oncolytics’ randomized North American breast cancer trials, IND-213 and BRACELET-1, respectively. In IND-213, HR+/HER2- breast cancer patients treated with pelareorep and paclitaxel showed a statistically significant, near doubling of overall survival compared to those treated with paclitaxel alone. BRACELET-1, an ongoing phase 2 study evaluating pelareorep-paclitaxel combination therapy with and without a checkpoint inhibitor, is on track for a top-line data readout in Q4 2022 that will inform the design of a registrational study in the United States. Final results from the Chinese bridging trial are expected to accelerate pelareorep’s development in territories such as China, Hong Kong, and Macau, by allowing Adlai Nortye to include data from IND-213 and BRACELET-1 in future submissions to regulators in these jurisdictions.

"The territories covered by our partnership with Adlai Nortye represent an important component of our business development strategy, as China and the other areas in which Adlai Nortye anticipates commercializing pelareorep are among the largest in the world and growing rapidly," said Andrew de Guttadauro, President of Oncolytics Biotech U.S. and Global Head of Business Development. "With the bridging trial entering its final cohort less than six months after dosing began, Adlai is making major strides towards satisfying the regulatory criteria needed to accelerate pelareorep’s development in China. The trial also continues to generate positive safety data, which will serve us well as we collaborate with Adlai Nortye to advance pelareorep towards approval in key global markets."

About Breast Cancer
Breast cancer is the most common cancer in women worldwide, with over two million new cases diagnosed in 2018, representing about 25 percent of all cancers in women. It is the second leading cause of death from cancer in women in America, with an estimated 42,000 deaths in the U.S. in 20201. In China, breast cancer is now estimated to be the largest subtype of cancer among women, with over 416,000 cases and over 117,000 deaths in 20202.

Breast cancer starts when cells in the breast begin to grow out of control. These cells usually form a tumor that can often be seen on an x-ray or felt as a lump. The malignant tumor (cancer) gets worse when the cells grow into (invade) surrounding tissues or spread (metastasize) to distant areas of the body.

On March 24, 2022 Fennec Pharmaceuticals Inc. (NASDAQ:FENC; TSX: FRX), a specialty pharmaceutical company, reported the resubmission of its New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for PEDMARKTM (a unique formulation of sodium thiosulfate (STS)) for the prevention of platinum-induced ototoxicity in pediatric patients one month to <18 years of age with localized, non-metastatic, solid tumors (Press release, Fennec Pharmaceuticals, MAR 24, 2022, View Source [SID1234610872]).

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"We appreciate the FDA’s comments during the resubmission process and look forward to working closing with the Agency during the NDA review," said Rosty Raykov, chief executive officer of Fennec Pharmaceuticals. "We are pleased to have reached this important step and Fennec remains committed to making PEDMARKTM available to reduce the risk of cisplatin induced ototoxicity in pediatric patients."

About PEDMARK

Cisplatin and other platinum compounds are essential chemotherapeutic agents for many pediatric malignancies. Unfortunately, platinum-based therapies cause ototoxicity, or hearing loss, which is permanent, irreversible and particularly harmful to the survivors of pediatric cancer.

In the U.S. and Europe, it is estimated that, annually, over 10,000 children may receive platinum-based chemotherapy. The incidence of ototoxicity depends upon the dose and duration of chemotherapy, and many of these children require lifelong hearing aids. There is currently no established preventive agent for this hearing loss and only expensive, technically difficult and sub-optimal cochlear (inner ear) implants have been shown to provide some benefit. Infants and young children that suffer ototoxicity at critical stages of development lack speech language development and literacy, and older children and adolescents lack social-emotional development and educational achievement.

PEDMARK has been studied by cooperative groups in two Phase 3 clinical studies of survival and reduction of ototoxicity, The Clinical Oncology Group Protocol ACCL0431 and SIOPEL 6. Both studies have been completed. The COG ACCL0431 protocol enrolled childhood cancers typically treated with intensive cisplatin therapy for localized and disseminated disease, including newly diagnosed hepatoblastoma, germ cell tumor, osteosarcoma, neuroblastoma, and medulloblastoma. SIOPEL 6 enrolled only hepatoblastoma patients with localized tumors.

The Marketing Authorization Application (MAA) for sodium thiosulfate (tradename PEDMARQSI) is currently under evaluation by the European Medicines Agency (EMA). PEDMARK has received Breakthrough Therapy and Fast Track Designation by the FDA in March 2018.

On March 24, 2022 Eli Lilly and Company (NYSE: LLY) reported that the U.S. Food and Drug Administration (FDA) has issued a complete response letter (CRL) for the Biologics License Application (BLA) for the investigational medicine sintilimab injection, a PD-1 inhibitor in combination with pemetrexed and platinum chemotherapy for the first-line treatment of people with nonsquamous non-small cell lung cancer (NSCLC) (Press release, Eli Lilly, MAR 24, 2022, View Source [SID1234610871]). Sintilimab is being developed by Innovent Biologics, Inc. (HKEX: 01801) and Lilly.

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The letter indicates that the review cycle is complete but the FDA is unable to approve the application in its current form, consistent with the outcome of the Oncologic Drugs Advisory Committee Meeting in February. The CRL includes a recommendation for an additional clinical study, specifically a multiregional clinical trial comparing standard of care therapy for first line metastatic NSCLC to sintilimab with chemotherapy utilizing a non-inferiority design with an overall survival endpoint.

Along with Innovent, Lilly is assessing next steps for the sintilimab program in the U.S.

About Sintilimab
Sintilimab, is an investigational PD-1 inhibitor developed by Innovent and Lilly. Sintilimab is a type of immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1 / PD-Ligand 1 (PD-L1) pathway, and reactivates T-cells to kill cancer cells. Innovent is currently conducting more than 20 clinical studies of sintilimab to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registrational or pivotal clinical trials.

In China, sintilimab, marketed as TYVYT (sintilimab injection), has been approved for:

The treatment of relapsed or refractory classic Hodgkin’s lymphoma after two lines or later of systemic chemotherapy
In combination with pemetrexed and platinum chemotherapy, for the first-line treatment of nonsquamous non-small cell lung cancer
In combination with gemcitabine and platinum chemotherapy, for the first-line treatment of squamous non-small cell lung cancer
In combination with BYVASDA (bevacizumab biosimilar injection) for the first-line treatment of hepatocellular carcinoma
Additionally, Innovent currently has regulatory submissions under review in China for sintilimab:

In combination with cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil for the first-line treatment of esophageal squamous cell carcinoma;
In combination with chemotherapy for the first-line treatment of unresectable, locally advanced, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma;
In combination with BYVASDA (bevacizumab biosimilar injection) and chemotherapy (pemetrexed and cisplatin) for EGFR-mutated nonsquamous NSCLC following EGFR-TKI treatment.
Sintilimab was included in China’s National Reimbursement Drug List (NRDL) for all four approved indications (listed above), according to the latest announcement from the China National Healthcare Security Administration ("NHSA").

On March 24, 2022 Collaborations Pharmaceuticals, Inc. (CPI) reported that they have entered into an agreement with Stepan Company to license CPI’s MegaTox machine learning software for predicting toxicology properties to aid their decision making and regulatory processes (Press release, Collaborations Pharmaceuticals, MAR 24, 2022, View Source [SID1234610870]).

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"We are honored to announce our first public licensee of our MegaTox software which we have developed with support from an SBIR from NIEHS." MegaTox provides curated machine learning models for ADME/Tox properties to scientists in chemical, consumer product, agrochemical, and pharmaceutical companies to enable them to predict properties and activities for molecules. The best-in-class machine learning algorithms are based upon over 25 years of ADME/Tox modelling research including not only human toxicology but also biodegradation, eco-toxicity and other properties of interest which can be used for read-across predictions. These machine learning models may assist in the regulatory decision-making process for molecules of commercial interest.

MegaTox is a curated data package that builds on the Assay Central software platform for building bespoke machine learning models using datasets from dozens to hundreds of thousands of molecules.

"We look forward to working with Stepan Company to enable them to more efficiently make toxicity hazard decisions on small molecules that are of interest to them" said Sean Ekins, CEO, CPI.

On March 24, 2022 Celsius Therapeutics, a biotechnology company leveraging its human tissue-based platform to develop precision medicines for patients with cancer and autoimmune disease, reported a summary of recent corporate highlights, including the nomination of its first clinical candidate for inflammatory bowel disease (IBD), an additional $83 million in financing and key initiatives for 2022 (Press release, Celsius Therapeutics, MAR 24, 2022, View Source [SID1234610869]).

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"2021 was a pivotal year of growth and advancement for Celsius," said Tariq Kassum, M.D., president and CEO of Celsius. "We have successfully scaled our SCOPE (Single Cell Observations for Precision Effect) platform to allow us to discover therapeutic targets of high interest in IBD and solid tumors. In addition, our approach allows us to identify patient stratification hypotheses based on cell types and cell signatures, expanding the reach of precision medicine into new territory. We have now performed single cell RNA sequencing of over 1,000 clinical tissue samples using this platform technology and our dataset continues to grow rapidly. We are excited to be fulfilling the vision of Celsius as we advance a potential first-in-class TREM1 antibody program for IBD and look to design smarter clinical studies based on biologic insights from our proprietary platform."

Announcement of lead clinical candidate for IBD

Celsius reported its first clinical candidate, CEL383, an anti-TREM1 antibody, for the treatment of IBD. TREM1, a myeloid target with a central role in IBD, was identified through single cell analysis of hundreds of clinical samples using machine learning algorithms via the company’s SCOPE platform. Through this approach, Celsius was able to identify and deeply characterize subsets of a pathogenic cell type that drive resistance to anti-TNF therapies and has defined a series of targets modulating behavior of these cell subtypes. TREM1, an amplifier of inflammation that resides at the intersection of the microbiome and the immune system, is the first of these targets.

The company anticipates filing an investigational new drug (IND) application with the U.S. Food and Drug Administration (FDA) within the next year, with a Phase 1 study expected to commence in early 2023. Celsius also plans to enable a precision medicine approach for CEL383 in IBD and has developed multiple biomarker hypotheses for evaluation in early clinical studies.

Progress in oncology pipeline

Beyond CEL383, Celsius has two ongoing drug discovery programs in oncology, both directed towards targets identified through analysis of hundreds of clinical solid tumor samples using the company’s SCOPE platform. The company plans to release more information on these programs in 2022. Additionally, the first candidate target in the company’s colorectal cancer collaboration with Servier, a global independent pharmaceutical group, has recently been selected, triggering a milestone payment to Celsius.

Additional $83 million in financing secured

Celsius also announced that it has raised $83 million in additional financing, comprised of a Series A extension and a Series B financing. The Series B financing was led by Casdin Capital, with participation from original investors Alexandria Venture Investments, GV, Heritage Provider Network and Third Rock Ventures and new investors Amgen Ventures, Amplitude Ventures, Catalio Capital, Co-Win Ventures, Fast Track Initiative, Section 32, as well as other undisclosed institutional investors. In connection with the completion of the Series B, Suzanne Jung Angell from Casdin Capital joined Celsius’ board of directors.

Key initiatives for 2022

Celsius expects 2022 to be an important year as the company continues to advance its mission to create new precision medicines for complex diseases such as autoimmunity and cancer. In 2022, the company plans to pursue the following key initiatives:

Continue to build the company’s clinically annotated, proprietary collection of human tissue data in IBD and cancer, and mine this dataset for new targets and patient stratification approaches
Prepare an IND for CEL383, the company’s lead antibody program for IBD
Advance the company’s oncology programs towards development candidate nomination
Nominate additional novel targets, derived from the company’s SCOPE platform, as drug discovery programs
Further progress the identification and validation of targets for colorectal cancer under the company’s ongoing drug discovery collaboration with Servier