On June 1, 2022 Teon Therapeutics (Teon), a clinical-stage biopharmaceutical company targeting metabolic signaling pathways and pioneering the development of G-Protein Coupled Receptor (GPCR) immuno-oncology therapies in difficult-to-treat cancers, reported the acceptance by the U.S. Food and Drug Administration (FDA) of Teon’s Investigational New Drug (IND) application for the study of TT-816 (Press release, Teon Therapeutics, JUN 1, 2022, View Source [SID1234615375]). TT-816 is a novel, oral cannabinoid CB2 receptor antagonist acting as an immune checkpoint inhibitor for the treatment of a broad range of solid tumors. The IND enables Teon to initiate its planned Phase 1/2 clinical trial designed to assess the dosing, tolerability and safety of TT-816 in patients with advanced cancers as a monotherapy and in combination with existing standard of care anti-PD-1 checkpoint inhibitors.

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"The FDA’s acceptance of the IND for TT-816 is an important validation of our approach to targeting a novel immune checkpoint pathway and marks a significant milestone for Teon," said Serge Messerlian, Chief Executive Officer of Teon. "As a highly-selective orally-administered checkpoint inhibitor, we believe that TT-816 has the promise to change the treatment landscape in many difficult-to-treat cancers, including lung, renal, and ovarian, and we are very pleased to begin evaluating its potential in the clinic."

The cannabinoid CB2 receptor belongs to the G protein-coupled receptor family. The cannabinoid CB2 receptor, selectively targeted by TT-816, is a peripheral receptor found predominantly in the immune system and regulates inflammation and the immune response. Elevated CB2 receptor expression is associated with worse overall survival[1-5] and aggressiveness of cancer.[6,7] Research has shown that CB2 receptor activation does not have any psychoactive properties unlike CB1 receptors which are located primarily in the brain.8

Preclinical results indicate that TT-816 enhances both the effect of NK cell tumor killing and T cell activation in vitro and increases both tumor infiltrating T cells and NK cells in vivo. TT-816 dose-dependently inhibits tumor growth in animal models, has an additive effect with anti-PD-1 in the ‘hot’ tumor model and acts synergistically with anti-PD-1 in the ‘cold’ tumor model where the anti-PD-1 alone had no effect.

"TT-816 is a novel immune checkpoint inhibitor that has demonstrated that it may have the potential to enhance both innate and adaptive immunity, synergize antitumor effects with current immune checkpoint inhibitor therapies​ and directly promote immune cell penetration into solid tumors," said Lina Yao, MD, PhD, Chief Scientific Officer of Teon. "TT-816 adds to Teon’s strong portfolio of highly-selective small molecules furthering the Company’s aim to advance first- or best-in-class cancer immunotherapies to patients."

Initiation of the Phase 1/2 TT-816 clinical trial is on track for third quarter 2022.

About TT-816
TT-816 is a first-in-class, oral cannabinoid CB2 receptor antagonist acting as an immune checkpoint inhibitor and is highly selective for the CB2 receptor versus the CB1 receptor. By inhibiting the actions of the CB2 receptors found in many difficult-to-treat cancers, including lung, renal, and ovarian, TT-816 has the potential to enhance immune response to treat solid tumors.

Targeting GPCR for Oncology – Tomorrow’s Treatments
With more than 700 approved drugs currently directed at them, GPCRs are the most commonly utilized target in today’s treatment paradigm, however, their potential in oncology and moreover, immuno-oncology, has yet to be leveraged. GPCRs control a broad range of cellular processes vital to the formation and progression of tumors. Small molecules are the most prevalent modulators of GPCR-targeted therapies. Insights into the roles of GPCRs in the tumor microenvironment and how they modulate both tumor-generating signal transduction pathways as well as interactions with immune system defense mechanisms may allow the pursuit of more novel GPCR-directed therapies.

On June 1, 2022 Flatiron HealthⓇ reported the appointment of Javier Jimenez, MD, MPH, as Chief Medical Officer, effective June 1, 2022 (Press release, Flatiron Health, JUN 1, 2022, View Source [SID1234615374]). In his new role, Dr. Jimenez will drive our vision for integrated evidence, harnessing new approaches to oncology evidence generation through Flatiron’s engaged care network and fit-for-purpose scientific methods and tools. His clinical expertise and proven leadership, as well as his extensive experience with real-world evidence, will continue to advance our scientific efforts and a future where we accelerate R&D and realize a more equitable and sustainable cancer care ecosystem. Dr. Jimenez succeeds Dr. Michael Vasconcelles, who will remain at Flatiron as a senior advisor through August 1, 2022.

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"Our commitment to reimagining the infrastructure of cancer care is unwavering. Mike has been instrumental in elevating and deepening the expertise and focus of our scientific, clinical, and regulatory efforts, establishing the foundational building blocks for our path forward. I would like to thank him for his significant contributions to Flatiron, and for doing so with dedication and passion," said Carolyn Starrett, Flatiron CEO. "I’m pleased to welcome Javier as our new Chief Medical Officer, joining our executive team. Javier is a visionary and one of the most deeply experienced healthcare leaders in the field of real-world evidence and novel study design. Flatiron is approaching our ten-year anniversary as a company, and we are more passionate than ever to lay the groundwork for a world where cancer research and care are integrated and accelerated globally. Javier has been pursuing a similar vision as a Flatiron customer since our inception."

Prior to Flatiron, Dr. Jimenez served as Executive Vice President, Real World Evidence and Late Phase at Syneos Health, with expertise spanning Clinical Development, Medical Affairs, Market Access and Product Commercialization. During his time at Syneos Health, Dr. Jimenez grew the RWE function, integrating RWE solutions experts, data and analytics, innovation and RWE clinical operations, while driving the RWD and analytics and technology company strategy. Dr. Jimenez started his journey in the pharmaceutical industry over twenty years ago, first spending sixteen years leading Medical Evidence, Observational Research, Epidemiology, Regulatory, and HTA teams across the US and Europe at AstraZeneca, while building Phase IIIb/IV design and delivery capabilities as well. Dr. Jimenez’s vast experience in Oncology includes leading AstraZeneca’s collaboration with ASCO (Free ASCO Whitepaper)’s CancerLinQ. Following his time at AstraZeneca, Dr. Jimenez spent four years building the RWE, Advance Analytics and Clinical Outcomes functions at Sanofi to support all Sanofi Global Business units, as well as developing technology, tools and capabilities to leverage RWD and generate insights. As an MD and Epidemiologist by training, Dr. Jimenez is a passionate champion and key opinion leader in the use of real-world data to transform regulatory decision making and in the design of novel clinical trials. Dr. Jimenez’s recent research contributions span hypoglycemia predictive modeling in patients with Type 2 diabetes and cardiovascular risk prevention, management in clinical practice settings and use of RWD to identify novel indications for products in development and build research-grade RWD.

"I am incredibly honored to join Flatiron, a global leader and pioneer in real-world evidence in oncology," said Dr. Jimenez. "Flatiron is at a transformative point in its trajectory, working to create a more modern, connected oncology ecosystem – and I am inspired to be a part of an organization that is committed to improving lives by learning from the experience of every cancer patient."

On June 1, 2022 Legend Biotech Corporation (NASDAQ: LEGN) (Legend Biotech), a global biotechnology company developing, manufacturing and commercializing novel therapies to treat life-threatening diseases, reported its first quarter 2022 unaudited financial results (Press release, Legend Biotech, JUN 1, 2022, View Source [SID1234615373]).

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"The year began with an exciting start as we received the company’s first-ever U.S. FDA approval for CARVYKTI," said Ying Huang, Ph.D., CEO of Legend Biotech. "This is the first of many cell therapies we hope to bring to patients, and we look forward to advancing the CARTITUDE clinical development program and our cell therapy pipeline over the rest of the year."

First Quarter 2022 Highlights and Recent Events

On February 28, 2022, the U.S. Food and Drug Administration (FDA) approved CARVYKTI for the treatment of adults with relapsed or refractory multiple myeloma who have received four or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody, marking the company’s first product approved by a health authority.
On May 26, 2022, the European Commission (EC) granted conditional marketing authorization of CARVYKTI for the treatment of adults with relapsed and refractory multiple myeloma who have received at least three prior therapies, including a proteasome inhibitor (PI), an immunomodulatory agent (IMiD) and an anti-CD38 antibody, and have demonstrated disease progression on the last therapy.
On April 21, 2022, Legend announced the achievement of a $50 million milestone under its collaboration agreement with Janssen Biotech, Inc. (Janssen) for CARVYKTI. Legend Biotech entered into an exclusive worldwide license and collaboration agreement with Janssen to develop and commercialize CARVYKTI in December 2017.
Legend Biotech engaged Ernst & Young LLP, located in the United States, as the company’s independent, registered public accounting firm for the audits of the Company’s financial statements and internal control over financial reporting for the fiscal year ending December 31, 2022.
CARTITUDE-6 (not yet recruiting; sponsored by the European Myeloma Network), a second Phase 3 trial in frontline multiple myeloma, was posted on clinicaltrials.gov. This Phase 3, randomized, open-label study compares daratumumab, bortezomib, lenalidomide and dexamethasone (DVRd) followed by cilta-cel vs. DVRd followed by autologous stem cell transplant (ASCT) in newly diagnosed, transplant-eligible patients with multiple myeloma.
On May 25, 2022, The FDA lifted its clinical hold of Legend Biotech’s Phase 1 clinical trial of LB1901, the company’s investigational autologous chimeric antigen receptor T-cell (CAR-T) therapy targeting malignant CD4+ T-cells for the treatment of adults with relapsed or refractory T-cell lymphoma (TCL).
On March 23, 2022, Legend Biotech was awarded Newcomer of the Year at the tenth annual Foreign Investment Trophy ceremony hosted by Flanders Investment & Trade (FIT) for its joint investment in a state-of-the-art manufacturing facility in Flanders with Janssen Pharmaceutica N.V.
Legend Biotech made the following management appointments: Lori Macomber, CPA, as Chief Financial Officer; Guowei Fang, Ph.D., as Senior Vice President, Global Head of Research and Early Development; and Marc L. Harrison, as Vice President and General Counsel.
Financial Results for First Quarter Ended March 31, 2022

Cash and Cash Equivalents, Time Deposits, and Short-Term Investments

As of March 31, 2022, Legend Biotech had approximately $796.0 million of cash and cash equivalents, deposits and short-term investments.

Revenue

Revenue for the three months ended March 31, 2022 was $40.8 million compared to $13.7 million for the three months ended March 31, 2021. The increase of $27.1 million was primarily due to revenue recognition from additional milestones achieved. Legend Biotech has not generated any revenue from product sales to date.

Research and Development Expenses

Research and development expenses for the three months ended March 31, 2022 were $81.3 million compared to $71.1 million for the three months ended March 31, 2021. This increase of $10.2 million was primarily due to a higher number of clinical trials with more patients enrolled and a higher number of research and development activities in cilta-cel and for other pipelines in the first quarter of 2022.

Administrative Expenses

Administrative expenses for the three months ended March 31, 2022 were $12.7 million compared to $8.7 million for the three months ended March 31, 2021. The increase of $4.0 million was primarily due to Legend Biotech’s expansion of supporting administrative functions to facilitate continuous research and development activities as well as activities to establish elements of a commercialization infrastructure.

Selling and Distribution Expenses

Selling and distribution expenses for the three months ended March 31, 2022 were $21.3 million compared to $13.4 million for the three months ended March 31, 2021. This increase of $7.9 million was primarily due to increased costs associated with commercial preparation activities for cilta-cel.

Other Income and Gains

Other income and gains for the three months ended March 31, 2022 were $1.0 million compared to $0.7 million for the three months ended March 31, 2021. The increase of $0.3 million was primarily due to more interest income earned in first quarter of 2022.

Other Expenses

Other expenses for the three months ended March 31, 2022 were $1.5 million compared to $2.0 million for the three months ended March 31, 2021. The decrease was primarily due to less foreign currency exchange loss in first quarter of 2022.

Finance Costs

Finance costs for the three months ended March 31, 2022 were $1.0 million compared to $0.04 million for the three months ended March 31, 2021. The increase was primarily due to interest for advance funding, which is comprised of interest on interest-bearing borrowings funded by Janssen under the parties’ collaboration agreement.

Fair Value Gain of Warrant Liability

Fair value gain of warrant liability for the year ended March 31, 2022 was $34.9 million caused by changes in the fair value of a warrant that Legend Biotech issued to an institutional investor through a private placement transaction in May 2021 with an initial fair value of $81.7 million at the issuance date. The warrant was assessed as a financial liability with a fair value of $87.9 million as of December 31, 2021 and a fair value of $53.0 million as of March 31, 2022.

Loss for the Period

For the three months ended March 31, 2022, net loss was $41.1 million, or $0.13 per share, compared to a net loss of $80.9 million, or $0.30 per share, for the three months ended March 31, 2021.

On June 1, 2022 InterVenn Biosciences, a clinical technology company leveraging glycoproteomics to transform the future of healthcare, reported that it has joined the Worldwide Innovative Network (WIN) Consortium and the Foundation for the National Institutes of Health’s Biomarker Consortium (Press release, InterVenn Biosciences, JUN 1, 2022, View Source [SID1234615372]). InterVenn’s innovation in glycoproteomic-based liquid biopsies and translational research provides novel strategies and new tools to improve patient care, advance clinical trials, accelerate biomarker discovery, and enhance precision oncology.

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"We are privileged and excited about becoming members of both the Biomarker Consortium of FNIH and the WIN consortium," said Klaus Lindpaintner, M.D., MPH, InterVenn Distinguished Scientist and representative on both organizations. "As we at InterVenn are advancing glycoproteomics as a new and powerful discipline to the clinic in oncology and beyond, being part of these networks will be instrumental in reaching patients and caregivers, making them aware of our platform and realizing its potential. We look forward to close interactions with both organizations and their members to explore collaborative projects."

On June 1, 2022 SynDevRx, Inc. reported the opening of a first-of-its-kind Phase 1b/2 study for patients with triple-negative breast cancer and baseline insulin resistance, testing the novel study drug evexomostat (SDX-7320) in combination with standard-of-care treatment Halaven (eribulin, Esai) (Press release, SynDevRx, JUN 1, 2022, View Source [SID1234615371]). Evexomostat is among the first anti-cancer therapeutics being developed specifically for cancer patients with baseline metabolic dysfunction (obesity, type 2 diabetes and pre-diabetes). The clinical research study is being conducted in collaboration with New York’s Memorial Sloan Kettering Cancer Center (MSK).

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Insulin resistance, also known as hyperinsulinemia, is a condition that can go undetected until a patient develops overt type two diabetes mellitus (T2D) or elevated HbA1c. Insulin controls blood glucose levels but is also a potent growth hormone. It has been widely reported that high insulin levels in the presence of certain cancers, like breast cancer1, can cause the tumors to grow faster, become more difficult to treat and lead to premature cancer progression with worse patient outcomes2. The aim of this research study is to explore the impact of targeting insulin and improving insulin resistance in combination with standard-of-care therapy on patients’ treatment response and outcomes. It is the first prospective study using a clinical therapeutic designed specifically to address this critical, yet grossly understudied aspect of cancer progression.

Dr. Neil Iyengar, MD, an MSK breast medical oncologist and principal investigator of this study, has been at the forefront of researching the negative influences that dysregulated metabolic hormones, like insulin, play in cancer patients’ treatment outcomes.

"Metabolic hormones play an important role in cancer establishment and progression, and are likely deterministic to patients’ clinical outcomes," Dr. Iyengar said. "The area of metabo-oncology research, historically overlooked, has gained momentum over the past several years, and may soon emerge as an essential aspect of cancer treatment. It is known that a patient’s metabolic health status impacts survival after cancer diagnosis, and in some cases, how well and for how long cancer treatment is effective."

"In a previous study, evexomostat (SDX-7320) demonstrated potent effects on elevated insulin levels in late-stage cancer patients, while preventing new metastases in several patients and with an acceptable safety profile," said Bradley Carver, co-founder and Chief Executive Officer of SynDevRx. "While the focus of this clinical study is targeting insulin levels and the impacts on TNBC progression, the additional anti-angiogenic effects of evexomostat (SDX-7320) also seen in a phase 1 study may independently enhance clinical benefits for patients. Further, oncologists typically don’t consider their patients’ metabolic health when designing treatment regimens. This study could change that. Dr. Iyengar’s trailblazing research and deep understanding of the metabo-oncology patient population, along with MSK’s exceptional reputation for outstanding and innovative research is the perfect opportunity to showcase the multi-faceted effects of evexomostat (SDX-7320) for breast cancer patients," said Bradley Carver.

"SynDevRx is at the forefront of metabo-oncology research and drug development, and we appreciate all the efforts from the team at MSK to bring this new experimental treatment paradigm to patients," Carver continued. "Dr. Iyengar’s unique experience integrating patients’ metabolic health with their cancer treatment has resulted in a study design that we believe could lead to future clinical practices that incorporate patients’ insulin levels and overall metabolic health into their cancer treatment regimens."

"SynDevRx is establishing global collaborations with leading research institutions focused on the downstream effects that obesity and dysregulated metabolic hormones have on cancer progression and metastasis. We invite other researchers to work with us as we untangle these complex and critical interactions between cancer and dysregulated metabolic hormones," said SynDevRx’s co-founder and Chief Business Officer James Shanahan.

Gallagher, E.J., et al., Hyperinsulinaemia in cancer. Nat Rev Cancer 20, 629–644 (2020)
Yee LD, et al., Metabolic Health, Insulin, and Breast Cancer: Why Oncologists Should Care About Insulin. Front. Endocrinol. 11:58 (2020).
About Evexomostat (SDX-7320)

Evexomostat (SDX-7320) is among the first drugs being developed specifically for cancer patients with metabolic complications, such as obesity, diabetes, high blood glucose or HbA1c, pre-diabetes or insulin/leptin resistance. For certain tumor types, metabolic hormones stimulate oncogenic pathways, making the cancer more aggressive and deadlier. Evexomostat acts by binding irreversibly to its target enzyme MetAP2, triggering downstream improvements in the metabolic hormones insulin, leptin and adiponectin, regulation of key lipids, and inhibition of the important angiogenic proteins bFGF and VEGF-C, as was demonstrated in a Phase 1 clinical study in late-stage cancer patients. In preclinical studies, evexomostat also directly inhibited multiple cell cycle signaling pathways, provided synergistic anti-tumor effects in combination with a PI3K inhibitor, reduced angiogenesis, controlled aberrant metabolic hormone signaling, and reversed obesity-induced immune suppression within the tumor micro-environment of tumor-bearing obese mice. Evexomostat is being developed for use in combination with clinically indicated standard-of-care cancer therapies for breast and other tumor types.