On January 30, 2023 Hervor Therapeutics reported the company received HV-101 IND clearance for Phase I/II Clinical Trial from NMPA (Press release, Hervor Therapeutics, JAN 30, 2023, View Source [SID1234638949]). HV-101 is an process-optimized, autologous unmodified Tumor-infiltrating lymphocyte (TIL) product fully developed at Hervor. Comparing to conventional TIL product, HV-101 has significant more percentage of stem-progenitor T cells and better functionality.

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In the coming phase I/II clinical study, the company will investigate the safety, tolerability, and preliminary Efficacy of HV-101 for patients with recurrent or metastatic solid tumors.

On January 30, 2023 NEC reported its Consolidated Financial Results for the Nine-month Period Ended December 31, 2022 (Press release, NEC, JAN 30, 2023, View Source [SID1234632909]).

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On January 30, 2023 University of Chicago reported that the George Shultz Innovation Fund (GSIF), managed by the Polsky Center for Entrepreneurship and Innovation, recently selected Riptide Therapeutics, a biopharmaceutical startup led by University of Chicago and Northwestern University researchers, as a Fall 2022 cohort award winner (Press release, University of Chicago, JAN 30, 2023, View Source [SID1234632030]).

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The company, launched in November 2021, aims to develop a therapeutic platform that helps make the body more responsive to cancer treatments. Grant Frost leads the startup and acts as its chief scientist. The team includes Steve Kron, professor of molecular genetics and cell biology at UChicago, and Karl Scheidt, professor of chemistry and pharmacology at Northwestern University.

"We are elated that the GSIF committee sees the potential in our therapeutic approach," said Frost. "This award provides Riptide with traction that should catalyze further investment towards our immediate drug development and future patient impact goals."

Riptide’s technology builds off a 2009 Nobel Prize-winning discovery that identified the enzyme telomerase, a crucial component of cancer biology. Telomerase, which isn’t expressed in healthy cells, allows cancer cells to replicate indefinitely, making them in essence immortal. Scientists heralded this discovery as a route for curing cancer. If they could find a way to target the enzyme and turn this mechanism off, the disease would stop progressing and existing cancer cells would simply die off.

Achieving this aim in clinic, though, has proven difficult – long-term inhibition of telomerase was shown to be toxic and wasn’t effective in more advanced cancers. Knowing this, the team at Riptide has taken a different approach towards realizing the potential of telomerase as a cancer drug target. Their focus dials in on telomerase’s role in cancer’s resistance to therapy.

First, the chemistry team at Northwestern designed a potent synthetic molecule called RTTX401, that is based off a naturally occurring telomerase inhibitor that uses a distinct mechanism of action compared to past drug development efforts. Next, the cancer biology team at UChicago used the new inhibitor not as a treatment on its own, but to sensitize tumors to existing therapies such as radiation and chemotherapy. With this approach, the team not only saw significant improvement to radiation response in mice models, but also the activation of the immune system against the tumors.

"Our inhibitors plus radiation effectively destroyed the tumors," said Scheidt. "We think this development of turning telomerase into an immuno-oncology target could have wide-ranging impact in cancer treatment."

The company, which has participated in numerous Polsky Center programs including I-Corps and Compass, is looking to partner with investors to begin preclinical development of its telomerase inhibitor, and then eventually move to testing in clinical trials.

"While we are hopeful that treating cancer patients with telomerase inhibitors to sensitize their tumors to radiation will be found safe and then shown to be effective, there will still be much more to do," said Kron. "However, it may not be long before physicians can offer this as an alternative to patients unlikely to benefit from current immunotherapy."

Riptide Therapeutics joins Alnair Therapeutics as the Fall 2022 GSIF cohort winners. Both will receive a $175,000 investment from the Fund.

During the GSIF process, teams received guidance and dedicated support from the Polsky Center, business experts, an advisory committee, and student Innovation Fund Associates who are training in venture capitalism.

"The GSIF is a venture-philanthropy fund, managed as an evergreen impact fund," said Ozge Guney Altay, director of Investment Strategy for Polsky Deep Tech Ventures. "Our mission and our challenge are one and the same: identify investment opportunities that not only generate significant financial returns, but also create lasting impact for humankind. We believe in all the companies that engage with us and are proud to have the opportunity to support them on their journeys."

To date, the Fund has invested $9 million in 94 companies that have gone on to raise $412 million in follow-on funding. Companies launched with the fund’s support include Onchilles Pharma, ExplORer Surgical, ClostraBio, Esya Labs, and Super.tech.

On January 1, 2023 The George Shultz Innovation Fund (GSIF), managed by the Polsky Center for Entrepreneurship and Innovation, reported that it recently selected oncology startup Alnair Therapeutics as a Fall 2022 cohort award winner (Press release, University of Chicago, JAN 30, 2023, View Source [SID1234632028]).

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The company, launched in September 2022, aims to develop a platform technology that improves the delivery of drugs to difficult-to-treat cancers. Xiaoyang Wu, associate professor of cancer research and stem cell biology at the University of Chicago, leads the startup.

Wu has a team of advisors from the Polsky Compass Deep Tech Accelerator that includes Anh Nguyen, Booth’11, vice president and R&D therapeutic head at Asklepios BioPharmaceutical; Aziz Alam, senior director of regulatory affairs at Kinnate Biopharma; and Sanjeev Thohan, senior vice president of nonclinical development at Alterome Therapeutics.

"We are extremely grateful to Polsky and to the Innovation Fund for their continued support bringing this technology to the next stage," Wu said. "The connections they enable and the expertise they provide are truly essential to the success of our development program."

Wu’s drug delivery platform addresses a major issue in cancer treatment. Currently, less than 1 percent of administered cancer drugs gets to the tumor site, and when they do, they’re not at a sufficient concentration to have an effect. This may result in cancer relapse and recurrence.

To overcome this, Wu uses a hallmark of cancer metabolism known as the "Warburg effect" to better target tumors and deliver drugs at effective levels.

"Uniquely, cancer cells run on lactate as a fuel source, and these levels of lactic acid are orders of magnitude higher than in healthy cells," he explains. "Our platform carries and delivers drugs directly to cancers by targeting the higher lactate levels within the tumor microenvironment. Further, to tailor drug delivery, it allows you to tune a threshold for when you want to release the cancer drug, at lower or higher lactate concentrations."

The first-in-class drug delivery platform is designed to work with many of today’s treatments, including oncolytic, targeted, immune and hormone therapies. Numerous preclinical trials have demonstrated significant increases in both tumor targeting and drug penetration, resulting in improved survival.

"We have done preclinical studies in mouse models that have shown significant improvement in survival," Wu said. "For instance, in triple negative breast cancer – an aggressive cancer with fewer treatment options that makes up about 15 percent of all breast cancers – we saw rates of survival 3.5 times versus conventional therapy. Even if we get a fraction of this benefit in future studies, it’s exceedingly promising."

Wu, who has also participated in Polsky’s Compass program, is looking to partner with investors to begin preclinical development of the platform, and then eventually move to a Phase 1 clinical trial.

Alnair Therapeutics joins Riptide Therapeutics as the Fall 2022 GSIF cohort winners. Both will receive a $175,000 investment from the Fund.

During the GSIF process, teams received guidance and dedicated support from the Polsky Center, business experts, an advisory committee, and student Innovation Fund Associates who are training in venture capitalism.

"The GSIF is a venture-philanthropy fund, managed as an evergreen impact fund," said Ozge Guney Altay, director of investment strategy for Polsky Deep Tech Ventures. "Our mission and our challenge are one and the same: identify investment opportunities that not only generate significant financial returns, but also create lasting impact for humankind. We believe in all the companies that engage with us and are proud to have the opportunity to support them on their journeys."

To date, the Fund has invested $9 million in 94 companies that have gone on to raise $412 million in follow-on funding. Companies launched with the fund’s support include Onchilles Pharma, ExplORer Surgical, ClostraBio, Esya Labs and Super.Tech.

On January 30, 2023 Daiichi Sankyo (TSE: 4568) reported that the first patient has been dosed in the global, randomized TROPION-Lung07 phase 3 trial evaluating datopotamab deruxtecan (Dato-DXd) in combination with pembrolizumab with or without platinum chemotherapy, in patients with previously untreated advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) with PD-L1 expression less than 50% (TPS<50%) and without actionable genomic alterations (Press release, Daiichi Sankyo, JAN 30, 2023, View Source [SID1234626656]).

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Datopotamab deruxtecan is a specifically engineered TROP2 directed DXd antibody drug conjugate (ADC) being jointly developed by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN).

Among patients with NSCLC, nearly half are diagnosed at an advanced stage and generally have a poor prognosis.1,2,3 While first-line treatment with pembrolizumab or other checkpoint inhibitors, with or without chemotherapy, has improved outcomes in patients with NSCLC without actionable genomic alterations, disease progression still occurs in the majority of patients.4,5

"Metastatic non-squamous non-small cell lung cancer remains a challenge because the majority of patients experience disease progression following their initial treatment, underscoring the need for more effective treatment options in the first-line setting," said Mark Rutstein, MD, Global Head, Oncology Clinical Development, Daiichi Sankyo. "The TROPION-Lung07 trial will assess the potential of the combination of datopotamab deruxtecan and pembrolizumab with and without chemotherapy, to evaluate whether this combination may be a more effective standard treatment option than the current standard of care for patients in the first-line setting."

"The combination of datopotamab deruxtecan with a checkpoint inhibitor with or without chemotherapy, has shown increased activity and a manageable safety profile in early trials, including TROPION-Lung02," said Cristian Massacesi, MD, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca. "With this initiation, TROPION-Lung07 becomes the third phase 3 trial in our evaluation of these investigational combinations for the first-line treatment of patients with non-small cell lung cancer, across PD-L1 segments and tumor histologies."

TROPION-Lung07 is the third clinical trial collaboration and supply agreement between Daiichi Sankyo and AstraZeneca with a subsidiary of Merck & Co., Inc., Rahway, NJ., USA to evaluate the combination of datopotamab deruxtecan and pembrolizumab. Previous clinical trial collaboration agreements were entered in October 2021 for the TROPION-Lung08 phase 3 trial and May 2020 for the TROPION-Lung02 phase 1b trial.

About TROPION-Lung07
TROPION-Lung07 is a global, randomized, open-label, phase 3 trial assessing the efficacy and safety of datopotamab deruxtecan in combination with pembrolizumab with or without platinum chemotherapy compared with pembrolizumab and platinum chemotherapy in patients with previously untreated, advanced or metastatic non-squamous NSCLC with less than 50% programmed death-ligand (PD-L1) expression (tumor proportion score [TPS] < 50%) and without actionable genomic alterations. Eligible participants in the three-arm study will be randomized in a 1:1:1 ratio to the following intervention arms: Arm A (datopotamab deruxtecan [6 mg/kg] plus pembrolizumab 200 mg IV plus platinum chemotherapy every three weeks), Arm B (datopotamab deruxtecan [6 mg/kg] plus pembrolizumab 200 mg IV every three weeks), and Arm C (pembrolizumab 200 mg IV plus pemetrexed [500 mg/m2] plus platinum chemotherapy every three weeks).

The primary endpoints of TROPION-Lung07 are progression-free survival (PFS) as assessed by blinded independent central review and overall survival. Secondary endpoints include objective response rate, duration of response, time to response, disease control rate as assessed by both investigator and blinded independent central review, PFS as assessed by investigator, PFS2 and safety.

TROPION-Lung07 will enroll approximately 975 patients at sites in North America, South America, Europe, Asia and Oceania. For more information visit ClinicalTrials.gov.

About Non-Small Cell Lung Cancer Without Actionable Genomic Alterations
Lung cancer is the second most common cancer and the leading cause of cancer-related mortality worldwide.1 NSCLC is diagnosed at an advanced stage in nearly 50% of patients and often has a poor prognosis with worsening outcomes after each line of subsequent therapy.6,7,8

While the introduction of targeted therapies and checkpoint inhibitors in recent years have improved outcomes for patients with advanced NSCLC, the majority of tumors do not have known actionable genomic alterations.7,8,9,10 The current standard of care in the first-line treatment of patients with advanced NSCLC without actionable genomic alterations consists of checkpoint inhibitors with or without platinum-based chemotherapy based on PD-L1 expression. While these therapies may improve survival, at least 40% to 60% of patients experience disease progression, underscoring the need for new therapeutic approaches and options.11,12,13,14

TROP2 (trophoblast cell-surface antigen 2) is a transmembrane glycoprotein that is widely expressed in several types of tumors, including NSCLC.15,16,17,18 TROP2 is expressed across all lung cancer subtypes with the highest expression seen in the majority of adenocarcinoma and squamous cell carcinoma (the most common forms of NSCLC).19 No TROP2 directed therapies are currently approved for the treatment of patients with NSCLC.19,20,21

About Datopotamab Deruxtecan (Dato-DXd)
Datopotamab deruxtecan (Dato-DXd) is an investigational TROP2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, datopotamab deruxtecan is one of the three lead ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programs in AstraZeneca’s ADC scientific platform. Datopotamab deruxtecan is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads, an exatecan derivative, via tetrapeptide-based cleavable linkers.

A comprehensive development program called TROPION is underway globally with more than 10 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple tumors including NSCLC, triple negative breast cancer and HR positive, HER2 low or negative breast cancer. Trials in combination with other anticancer treatments are also underway.