On January 11, 2021 Zymeworks Inc. (NYSE: ZYME), a clinical-stage biopharmaceutical company developing multifunctional biotherapeutics, reported its key accomplishments in 2020 and updated its corporate priorities (Press release, Zymeworks, JAN 11, 2021, View Source [SID1234573790]).

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"2020 was a leap forward for our lead clinical program in terms of a potential first approval and future approvals," said Ali Tehrani, Ph.D., President and CEO at Zymeworks. "The launch of our first pivotal trial and achievement of Breakthrough Therapy designation for zanidatamab mark important milestones towards our accelerated commercialization strategy, and our new clinical partnerships further strengthen zanidatamab’s broad therapeutic profile. 2021 promises to be a data-rich year for both zanidatamab and ZW49 as we continue to demonstrate their potential to become foundational therapies in the treatment of HER2-expressing cancers."

2020 Achievements

Zanidatamab Enters Late-Stage Clinical Development with Accelerated Strategy

Zymeworks initiated a global pivotal trial (HERIZON-BTC-01) for zanidatamab monotherapy in patients with previously treated HER2 gene-amplified biliary tract cancer (BTC). This single arm trial is designed to support accelerated approval based on a primary endpoint of objective response rate and may enable submission of a Biologics License Application (BLA) as early as 2022.
Zanidatamab received additional drug review special designations in the U.S. and the European Union. The U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation for BTC and the European Commission (EC) granted Orphan Drug designation for gastroesophageal adenocarcinoma (GEA), expediting potential commercialization. Previously the FDA granted two Fast Track designations to zanidatamab, in BTC and GEA, in addition to Orphan Drug designations for BTC, GEA, and ovarian cancer.
Zanidatamab Data and Partnerships Continue to Support Broad Therapeutic Potential

Gastric Cancer: Clinical data from patients with refractory GEA treated with zanidatamab monotherapy as well as zanidatamab in combination with chemotherapy were updated and support plans to launch a second pivotal trial as 1st line treatment for advanced HER2-positive GEA in mid-2021 with partner BeiGene. These data will be updated as part of an oral presentation at the upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium, January 15, 2021.
Breast Cancer: Clinical collaborations were initiated to evaluate zanidatamab in combination with a CD47 blocker (ALX Oncology’s ALX148) in patients with advanced HER2‑expressing breast cancer and with a CDK4/6 inhibitor (Pfizer’s Ibrance) in patients with HER2‑positive, HR-positive breast cancer.
Endometrial Cancer: Zymeworks’ first investigator-led trial was initiated by Dr. Vicky Makker at Memorial Sloan Kettering Cancer Center. The Phase 2 trial will evaluate zanidatamab monotherapy in HER2-overexpressed advanced endometrial cancers and carcinosarcomas.
Clinical Advancement of HER2 Bispecific ADC, ZW49, for HER2 Expressing Cancers

ZW49 is being evaluated in a Phase 1 clinical trial as a treatment for patients with locally advanced or metastatic HER2-expressing cancers that have progressed following treatment with existing approved therapies, including HER2-targeted agents. Clinical studies continued in 2020 with dose escalation to determine the safety and efficacy profile of ZW49. Zymeworks will be providing a clinical progress update for ZW49 by webcast on Wednesday, January 27, 2021 at 4:30 pm ET.
Commercial, Clinical and Scientific Competencies Added to Leadership Team

Zymeworks welcomed key commercial, scientific and clinical development talent to the leadership team with the additions of Guowei Fang, Ph.D., as Senior Vice President, Research, James Priour as Senior Vice President, Commercial, Manny Duenas as Vice President, Global Value and Access, and Pamela Farmer, MD, as Vice President, Global Patient Safety.
Partnerships Advance: Milestone Payments Received and Deal Values Increase

Our partnerships continued to advance in 2020 with Iconic/Exelixis achieving a milestone for ZymeLink together with new and expanded Azymetric and EFECT collaborations with Merck and BMS. Zymeworks has nine active collaborations that could result in up to US$8.6 billion in potential milestone payments in addition to royalties on potential product sales.
Balance Sheet Strengthened and Cash Runway Extended

In early 2020, Zymeworks completed an oversubscribed public financing raising US$320.8 million, extending its runway into 2022 and potentially beyond. The Company also received non-dilutive capital from several of its pharmaceutical partners.
Updated Corporate Priorities

Complete enrolment of zanidatamab pivotal trial in HER2+ biliary tract cancer
Launch pivotal trial in 1st line HER2+ GEA and present supporting Phase 2 clinical data
Present data to support zanidatamab breast cancer development strategy
Advance ZW49 into and complete cohort expansion
Present data from new therapeutic programs and technology platforms

On January 11, 2021 Turning Point Therapeutics, Inc. (NASDAQ: TPTX), a precision oncology company developing next-generation therapies that target genetic drivers of cancer, and Zai Lab (NASDAQ: ZLAB; HKEX: 9688), an innovative commercial-stage biopharmaceutical company, reported an expansion of their collaboration (Press release, Zai Laboratory, JAN 11, 2021, View Source [SID1234573787]).

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Under the terms of the new agreement, Zai Lab will obtain exclusive rights to develop and commercialize TPX-0022, Turning Point’s MET, SRC and CSF1R inhibitor, in Greater China, which includes mainland China, Hong Kong, Macau and Taiwan. Turning Point will receive a $25 million upfront payment, with up to approximately $336 million in potential development, regulatory and sales-based milestone payments. Turning Point will also be eligible to receive mid-teen- to low-twenty-percent royalties based on annual net sales of TPX-0022 in Greater China. In addition, Turning Point will have the right of first negotiation to develop and commercialize an oncology drug candidate discovered by Zai Lab.

This agreement builds on Zai Lab and Turning Point’s existing relationship under the exclusive licensing agreement announced by the companies in July 2020, under which Zai Lab gained the exclusive right to develop and commercialize Turning Point’s lead drug candidate, repotrectinib, in Greater China.

"The higher incidence of MET-driven cancers – particularly in gastric and lung cancer – in Asian countries led us to initiate the development of TPX-0022 in Greater China following our encouraging initial data from the Phase 1 SHIELD-1 study," said Athena Countouriotis, M.D., president and chief executive officer of Turning Point. "We have great confidence in Zai Lab as our partner to advance this important drug candidate in a key region of the world. Zai Lab also has a promising discovery pipeline and we are pleased to receive the right of first negotiation for a drug candidate from Zai’s discovery pipeline."

Dr. Samantha Du, Founder, Chairperson and Chief Executive Officer of Zai Lab, said, "Turning Point has assembled a formidable pipeline of next-generation oncology target therapies, and we are very pleased to broaden our global collaboration and strategic partnership. We believe TPX-0022 is a promising drug candidate that is also highly synergistic with our portfolio in gastric and lung cancer."

Jin Li, M.D., Professor, Chairman of Chinese Society of Clinical Oncology Foundation and Director of Department of Oncology, Tongji University Shanghai East Hospital said, "The initial safety and efficacy data for TPX-0022 are promising, and its novel mechanism to target MET, SRC and CSF1R encourages us to investigate its therapeutic potential further. We are particularly interested in the early but promising findings in patients with MET-driven gastric cancer and look forward to advancing the study of TPX-0022 in this area of high unmet need in China."

Initial data from the SHIELD-1 study reported in a late-breaker oral presentation at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) symposium highlighted preliminary clinical activity, including objective responses across multiple tumor types and a generally tolerable safety profile.

About TPX-0022

TPX-0022 is an orally bioavailable multi-targeted kinase inhibitor with a novel three-dimensional macrocyclic structure that inhibits the MET, CSF1R (colony stimulating factor 1 receptor) and SRC kinases. TPX-0022 has completed IND-enabling studies and cleared its IND. During the second half of 2019, Turning Point initiated the SHIELD-1 Phase 1 clinical trial of TPX-0022 for the treatment of advanced or metastatic solid tumors with abnormal MET/HGF or CSF1R/SCF1R signaling.

MET is a receptor tyrosine kinase that binds with high affinity to hepatocyte growth factor (HGF). MET alterations, including point mutations, amplifications, fusions, exon 14 skipping, and the generation of HGF-MET autocrine loops have been reported in many cancers. MET amplification has been detected in up to 20 percent of non-small cell lung cancer patients with EGFR mutations who acquired resistance to Iressa (gefitinib), Tarceva (erlotinib) or Tagrisso (osimertinib) treatment. SRC is a kinase involved in the MET signaling pathway. Inhibition of SRC has the potential to reduce or abolish the upregulation of HGF. Targeting CSF1R leads to the modulation of tumor-associated macrophages (TAMs), a type of immune cell that suppresses the T-cell mediated anti-tumor immune response, which is a promising therapeutic strategy for TPX-0022 as a single agent or in combination with standard of care chemotherapy and immunotherapy in various solid tumors.

On January 11, 2021 Synlogic, Inc. (Nasdaq: SYBX), a clinical stage company bringing the transformative potential of synthetic biology to medicine, reported that significant clinical milestones for 2021 and provided an overview of recent progress (Press release, Synlogic, JAN 11, 2021, View Source [SID1234573785]).

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"With three programs in clinical trials, multiple proof of concept opportunities, and a preclinical portfolio advancing rapidly towards the clinic, Synlogic is poised for success with a number of data readouts coming in 2021," said Aoife Brennan, M.B. Ch.B., Synlogic’s President and Chief Executive Officer. "2020 was a year we will not forget. Despite the external challenges, the Synlogic team moved our programs forward with grit and resilience. We enter 2021 with momentum and the opportunity to truly see the potential of novel Synthetic Biotic medicines to make a meaningful difference in patients’ lives."

Synlogic anticipates clinical proof of concept data in 2021 across two metabolic programs, SYNB1618 for the treatment of Phenylketonuria (PKU) and SYNB8802 for the treatment of Enteric Hyperoxaluria, as well as continued advancement of SYNB1891 for the treatment of solid tumors and lymphomas.

Execution Across Clinical Pipeline: Metabolic Programs

Progression of a proof of concept Phase 2 clinical trial of SYNB1618 for the treatment of Phenylketonuria (PKU)
SYNB1618 is an investigational drug composed of a Synthetic Biotic medicine designed to consume phenylalanine (Phe) in the gastrointestinal (GI) tract for the treatment of PKU in patients regardless of age or disease type.
A solid oral formulation of SYNB1618 has been shown to metabolize Phe in the GI tract in a healthy volunteer study.
The SynPheny-1 study evaluates plasma Phe lowering of SYNB1618 in adult PKU patients who do not benefit from, or do not tolerate, existing therapies such as Kuvan or Palynziq.
Synlogic anticipates data from SynPheny-1 will be available mid- 2021.

Progression of a Phase 1 clinical study of SYNB8802 for the treatment of Enteric Hyperoxaluria
SYNB8802 is an investigational drug composed of a Synthetic Biotic medicine designed to consume oxalate in the GI tract and lower urinary oxalate levels, potentially reducing kidney damage due to Enteric Hyperoxaluria.
In data presented at the American Society of Nephrology’s (ASN) 2020 Kidney Week, SYNB8802 was shown to reduce urinary oxalate in two animal models of Hyperoxaluria.
The Phase 1 clinical study evaluates the safety, tolerability, and potential for urinary oxalate lowering in healthy volunteers and patients.
The study has two parts: Part A is a multiple ascending dose study in healthy volunteers; Part B is a placebo controlled, cross-over design study in patients with Enteric Hyperoxaluria following Roux-n-Y gastric bypass surgery which provides an opportunity to demonstrate proof of concept.
Synlogic anticipates data from Part B of the study will be available mid-2021.
Execution Across Clinical Pipeline: Immunomodulation Programs

Advancement of SYNB1891 into combination arm dosing with PDL1 checkpoint inhibitor in ongoing Phase 1 study
SYNB1891 is an investigational drug composed of an intratumorally delivered Synthetic Biotic medicine designed to produce a STING agonist and act as a dual innate immune activator for the treatment of advanced solid tumors and lymphoma.
SYNB1891 is currently being evaluated in a Phase 1 study that has two parts:
Part A is a monotherapy arm that has enrolled four dose cohorts to date.
A maximum tolerated dose has not been reached and dose escalation continues.
Part A of the study has demonstrated target engagement and activation of the STING pathway.
Part B of the study will combine escalating dose levels of SYNB1891 with a fixed dose of the PD-L1 checkpoint inhibitor atezolizumab, to establish a recommended Phase 2 dose for the combination regimen.
Synlogic anticipates additional data from cohorts in both arms will be available in mid to late 2021.
Preclinical Roadmap

Synlogic continues to advance preclinical programs including additional effectors for immune-oncology; immune regulation targets for treatment of inflammatory bowel disease and other inflammatory disorders; and additional undisclosed rare metabolic diseases.
Further updates on these programs will be shared as they advance towards the clinic.
2020 Corporate Milestones

Synlogic strengthened leadership with the following appointments:
Synlogic appointed Dr. David Hava, Ph.D., as Chief Scientific Officer. Dr. Hava brings over a decade of senior experience in research and development to Synlogic, including deep academic expertise in pillars of synthetic biology.
Synlogic promoted Antoine ‘Tony’ Awad to Chief Operating Officer. Mr. Awad brings over 15 years of experience in the biotechnology and pharmaceutical industry with substantial experience in the development and manufacturing of novel therapeutics from pre-IND studies through global commercialization.
Synlogic appointed Michael Heffernan, seasoned entrepreneur and biopharmaceutical leader, and Dr. Michael Burgess, physician scientist and expert in translational development, to its board of directors.
Synlogic and Ginkgo Bioworks advanced their long-term strategic platform collaboration that provides expanded synthetic biology capabilities to Synlogic.
Ginkgo and Synlogic are collaborating on multiple efforts including metabolic and immunomodulation programs, and assessment of the potential application of Synthetic Biotics for vaccine development.
Synlogic ended the third quarter of 2020 with $102.0 million in cash, cash equivalents and short- and long-term investments and expects this will fund company operations through 2022 under its current plan.

On January 11, 2021 Surface Oncology (Nasdaq: SURF), a clinical-stage immuno-oncology company developing next-generation immunotherapies that target the tumor microenvironment, reported that Jeff Goater, chief executive officer, will participate in the upcoming H.C. Wainwright Bioconnect 2021 Conference, which will take place January 11–14 (Press release, Surface Oncology, JAN 11, 2021, View Source [SID1234573784]).

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The discussion will focus on Surface Oncology’s lead programs, SRF617 (targeting CD39) and SRF388 (targeting IL-27), as well as Surface’s emerging pre-clinical program, SRF114 (targeting CCR8). The discussion will be available on demand to conference attendees for the duration of the event beginning at 6:00 a.m. ET on Monday, January 11.

On January 11, 2021 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported program updates and announced key milestones for 2021, which are expected to substantially expand and advance the company’s clinical pipeline (Press release, ORIC Pharmaceuticals, JAN 11, 2021, View Source [SID1234573783]).

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"2020 was a transformational year for ORIC during which we significantly broadened the pipeline via internal discovery and business development efforts, expanded the team, and strengthened the balance sheet with the completion of an IPO and follow-on financing," said Jacob Chacko, M.D., president and chief executive officer. "These efforts have positioned us for a dynamic 2021, with our first data from two ongoing trials of our lead program ORIC-101 and three INDs/CTAs for our other product candidates, which represents a tremendous amount of development activity for a company at our stage."

Program Updates and 2021 Milestones

ORIC-101: Glucocorticoid Receptor (GR) Antagonist
ORIC-101 is a potent and selective GR antagonist, with two distinct mechanisms of action being evaluated in two Phase 1b trials in combination with: (1) Xtandi (enzalutamide) in metastatic prostate cancer and (2) Abraxane (nab-paclitaxel) in advanced or metastatic solid tumors.

The company announced today the completion of the Part I dose escalation portion of the Phase 1b trial of ORIC-101 in combination with enzalutamide in metastatic prostate cancer, by identifying the provisional recommended Phase 2 dose (RP2D) that will be used in the Part II expansion portion of the trial. The selection of the provisional RP2D was based upon the totality of safety, pharmacokinetic, and pharmacodynamic data demonstrating a well-tolerated regimen that achieved ORIC-101 exposures leading to demonstrable target engagement and GR inhibition. In the Part I dose escalation portion of the trial, patients were enrolled to evaluate daily dosing of ORIC-101 with doses ranging from 80 to 240 mg, in combination with daily dosing of 160 mg of enzalutamide. In the Part II dose expansion portion of the trial, up to 48 patients are expected to be enrolled and treated at the RP2D of 240 mg of ORIC-101 and 160 mg of enzalutamide on a continuous daily dosing schedule. Patients will be enrolled independent of GR status, with retrospective analysis of GR expression and other potentially predictive biomarkers. The company expects to report interim safety, efficacy, and translational data from this trial in the second half of 2021.
The Phase 1b trial of ORIC-101 in combination with nab-paclitaxel is now enrolling patients in the Part II dose expansion portion. In December 2020, the company announced the completion of the Part I dose escalation portion of ORIC-101 in combination with nab-paclitaxel in solid tumors, the selection of the RP2D, and the initiation of the dose expansion portion of the trial. For the Part II dose expansion portion of the trial, up to 132 patients are expected to be enrolled across four cohorts, including pancreatic ductal adenocarcinoma, ovarian cancer, triple negative breast cancer, and other advanced solid tumors. Patients in Part II of the trial will be treated at the RP2D of 160 mg of ORIC-101 continuous once daily dosing and 75 mg/m2 of nab-paclitaxel on days 1, 8, and 15 of a 28-day cycle, without requirement for prophylactic granulocyte colony-stimulating factor. Eligible patients must have previously progressed on a taxane-containing regimen and will be enrolled independent of baseline GR status, with retrospective analysis of GR expression and other potentially predictive biomarkers. The company expects to report interim safety, efficacy, and translational data from this trial in the first half of 2021.
ORIC-533: CD73 Inhibitor
ORIC-533 was designed to be a highly potent, orally bioavailable CD73 inhibitor and has demonstrated more potent adenosine inhibition in preclinical studies compared to an antibody approach and other small molecule CD73 inhibitors. ORIC-533 continues to progress in Investigational New Drug (IND) enabling studies and the company expects to file an IND with the Food and Drug Administration (FDA) in the first half of 2021. Having conducted a preclinical collaboration with an academic key opinion leader that generated compelling single agent activity in patient derived model systems in an undisclosed tumor type, the company plans to pursue a single agent clinical development path in this indication.

ORIC-944: PRC2 Inhibitor
ORIC-944, in-licensed in August 2020, is a potent and selective allosteric inhibitor of polycomb repressive complex 2 (PRC2), that targets its regulatory embryonic ectoderm development (EED) subunit and has demonstrated single agent efficacy in multiple enzalutamide-resistant prostate cancer models in preclinical studies. The company plans to conduct IND enabling studies and then file an IND with the FDA in the second half of 2021, with initial clinical development as a single agent in treatment-resistant prostate cancer.

ORIC-114: EGFR/HER2 Inhibitor
ORIC-114, in-licensed in October 2020, is a brain penetrant, orally bioavailable, irreversible inhibitor designed to selectively target EGFR and HER2 with high potency against exon 20 insertion mutations. ORIC-114 has demonstrated greater brain exposure in preclinical studies compared to other compounds being developed against exon 20 mutations and has shown strong antitumor activity in an EGFR-driven intracranial lung cancer model. The company plans to conduct IND enabling studies and then file a Clinical Trial Application (CTA) in South Korea in the second half of 2021.

Discovery Pipeline
In addition to the four product candidates, the company is leveraging its resistance platform in pursuit of multiple discovery research programs that focus on its expertise in precision oncology, hormone-dependent cancers, and key tumor dependencies. These programs highlight the company’s medicinal chemistry and structure-based drug design proficiency to target drivers of resistance in solid tumors like prostate, breast, and lung cancer that relapse with innate, acquired or bypass mechanisms of resistance. The company recently advanced one of these programs into lead optimization.

Anticipated 2021 Milestones

ORIC anticipates the following milestones in 2021:

ORIC-101: Report interim safety, efficacy, and translational data from ongoing combination trial with nab-paclitaxel in the first half of 2021
ORIC-101: Report interim safety, efficacy, and translational data from ongoing combination trial with enzalutamide in the second half of 2021
ORIC-533: File an IND in the first half of 2021
ORIC-944: File an IND in the second half of 2021
ORIC-114: File a CTA in the second half of 2021
Present additional preclinical and translational research data on ORIC-101, ORIC-533, ORIC-944, and ORIC-114 at scientific conferences in 2021
Financial Guidance

Cash, cash equivalents and marketable securities totaled $293.6 million as of December 31, 2020, which included gross proceeds of $133.3 million from the follow-on financing completed in November 2020. The company expects its cash, cash equivalents and marketable securities will be sufficient to fund its current operating plan into the second half of 2023.

Presentation and Webcast

Jacob Chacko, M.D., president and chief executive officer, will present a corporate overview at the 39th J.P. Morgan Healthcare Conference beginning at 12:40 p.m. PT on Tuesday, January 12, 2021. A live webcast will be available through the investor section of the company’s website at View Source A replay of the webcast will be available for 90 days following the event.