Innovent Announces the First Patient Dosed in the Phase 1 Study of IBI323 (Anti-LAG-3/PD-L1 Bispecific Antibody) in Patients with Advanced Malignant Tumors

On July 11, 2021 Innovent Biologics, Inc. (Innovent) (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of cancer, metabolic, autoimmune and other major diseases, reported that the first patient has been dosed in a Phase 1 study of IBI323, an anti-LAG-3/PD-L1 bispecific antibody (Press release, Innovent Biologics, JUL 11, 2021, View Source [SID1234584772]).

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The objective of this open-label, multi-center Phase 1 dose escalation and expansion study is to evaluate the safety, tolerability, potential optimal dosage and preliminary efficacy of IBI323 in patients with advanced malignant tumors whose cancer progressed on standard-of-care treatment. The trial is being conducted in China.

IBI323 is a recombinant LAG-3/PD-L1 bispecific antibody. Preclinical studies showed that IBI323 effectively blocks both the PD-1/PD-L1 and LAG-3 pathways and can generate more effective and durable activation of T lymphocyte activation than the combination of anti-PD-L1 monoclonal antibody and anti-LAG monoclonal antibody. Besides, through the bridging effect of bispecific antibody, tumor cells expressing PD-L1 can be drawn closer to T lymphocyte expressing LAG-3, thus forming stable TCR: MHC immune synapses and enhancing T lymphocyte activation. Therefore, IBI323 shows advantages compared with two drugs combination according to the mechanism. Recently, an article about IBI323’s bispecific antibody enhances tumor-specific immunity was published on Oncolmmunology.

Professor Caicun Zhou, Chief of Oncology Department of Shanghai Pulmonary Hospital Affiliated to Tongji University and Director of Cancer Institute of Tongji University Medical School, stated: "Although immune checkpoint inhibitors have shown promising results in the treatment of a wide range of tumors, there still remains many new challenges. Many patients inevitably develop drugs resistance and the efficacy of immune checkpoint inhibitors needs to be further enhanced. Therefore, it is of great value to develop the next generation of bispecific antibodies. LAG-3 is one of the most promising targets among cancer immunotherapy, combining innovative techniques for bispecific monoclonal antibody, we look forward to the results of IBI323 clinical trials. "

Dr. Hui Zhou, Senior Vice President of Clinical Development of Innovent, stated: "The LAG-3/PD-L1 bispecific antibody can specifically target both LAG-3 and PD-L1, block both the PD-1/PD-L1 and LAG-3 pathways, synergically enhance the activity of T lymphocyte and close the distance between tumor cells with high PD-L1 expression and T cells expressing LAG-3. The preclinical results have shown that compared with two monoclonal antibodies, IBI323 can further enhance the immune activation with improved convenience of administration. Therefore, the development of LAG-3/PD-L1 bispecific antibody will provide patients with a novel, comprehensive, effective and cost-saving treatment regimen. We hope that IBI323 will benefit more patients. "

About IBI323 (anti-LAG-3/PD-L1 bispecific antibody)

IBI323 is a recombinant LAG-3/PD-L1 bispecific antibody developed by Innovent Biologic. The IND of IBI323 has been approved by NMPA and we are actively conducting the clinical trial in China. We also plan to prepare an IND application with the U.S. Food and Drug Administration (FDA).

About the Phase 1 Study of IBI323 (CIBI323A101)

Conducted by Innovent in China, the CIBI323A101 trial is a Phase 1 open-label, multi-center study of the safety, tolerability and primary efficacy of IBI323 in patients with advanced solid tumors (ClinicalTrials.gov, NCT04916119).

Nucleix Presents Clinical Data at EAU21 Virtual Congress Which Demonstrates Promising Advances in the Care of Bladder Cancer Patients

On July 11, 2021 Nucleix, a liquid biopsy company revolutionizing cancer treatment by detecting the disease earlier, reported data from two abstracts featuring its Bladder EpiCheck test at the 36th Annual European Association of Urology (EAU) Virtual Congress (Press release, Nucleix, JUL 11, 2021, View Source [SID1234584771]).

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The first abstract titled, "Real world evidence of alternating cystoscopy/cytology with Bladder EpiCheck in NMIBC surveillance," shows the results of a pilot performed at Radboud University Medical Center evaluating the feasibility and clinical outcomes of alternating between cystoscopy/cytology and Bladder EpiCheck in non-muscle invasive bladder cancer (NMIBC) surveillance. To alleviate the burden of invasive and costly standard surveillance methods on patients, urine collection was performed at home and shipped to a central lab to perform the Bladder EpiCheck test. In the pilot analysis, patients with follow-up showed Bladder EpiCheck achieved 100% sensitivity for high-grade disease, with specificity of 88%, thereby avoiding 76% of unnecessary cystoscopies. Authors concluded this modified surveillance schedule was both safe and cost-effective due to Bladder EpiCheck’s high sensitivity for high-grade disease and high specificity.

"This is the first published evidence for using an alternating schedule of a urine marker, such as Bladder EpiCheck, and cystoscopy or cytology. Due to Bladder EpiCheck’s high sensitivity for high-grade disease and high specificity, and a well-planned infrastructure, all high-grade tumors, including muscle invasive tumors, were detected while avoiding 76% of unnecessary cystoscopies," said Fred Witjes, M.D., Professor of Medical Sciences at Radboud University Medical Center. "As a result of the pilot, Radboud University hospital has implemented this monitoring schedule as a routine for all NMIBC patients."

The second abstract titled, "DNA methylation urine biomarkers test (EpiCheck assay) in the diagnosis of upper tract urothelial carcinoma: results from a single-center prospective study," evaluated the performance of Bladder EpiCheck in the detection of upper urinary tract urothelial carcinoma (UTUC) among 80 consecutive patients undergoing ureteroscopy for the diagnosis, treatment or follow-up of UTUC. The study found that Bladder EpiCheck achieved a high-grade sensitivity of 95.8%; a high-grade negative predictive value of 97.2%; and a specificity of 80.6% in urine collected from the ureter-bladder junction, compared to 80.0%, 90.0% and 91.7% for cytology, respectively.

"It is very challenging to stage a UTUC with a biopsy, as we know that up to 30% of UTUC are understaged with this technique. This can be detrimental to the patient as high-grade UTUC, if missed, can progress to metastases very quickly. Alternatively, if a patient with a low-grade tumor is mistaken for high-grade, or high-grade disease can’t be ruled-out, they might undergo unnecessary procedures such as removal of the ureter and kidney of that side," said Dr. Alberto Breda, head of the oncological urology unit and the kidney transplant team in Fundació Puigvert, Barcelona, Spain. "The results of this study show that Bladder EpiCheck can be a useful tool in the UTUC setting and could play a crucial role in the diagnosis and follow-up of the disease, particularly in ruling-out high-grade disease."

About Bladder EpiCheck

Bladder EpiCheck provides patients and clinicians with a simple, objective urine test to detect recurrence of bladder tumors. The test analyzes subtle disease-specific changes in DNA methylation markers, allowing for the detection of 92% of the high-risk (non Ta-LG) cancers. Bladder EpiCheck demonstrated negative predictive value (NPV) of 99% for high-risk cancer, meaning that when receiving a negative Bladder EpiCheck result, there is 99% chance that no high-risk cancer is present1. Bladder EpiCheck is intended for use as a noninvasive method for monitoring of tumor recurrence in conjunction with cystoscopy in patients previously diagnosed with bladder cancer. Bladder EpiCheck is CE-marked and available in Europe. The test is not available for sale in the United States.

Alpha Tau & Healthcare Capital Corp. to Combine and Create A $1-Billion Publicly Traded Company

On July 11, 2021 Alpha Tau reported that proprietary Alpha DaRT is designed to deliver uniquely potent alpha radiation to destroy solid tumors with localized precision, sparing surrounding healthy tissue, thereby maintaining cancer patients’ quality of life (Press release, Alpha Tau Medical, JUL 11, 2021, View Source [SID1234584768]). Alpha DaRT has recently received FDA’s Breakthrough Device Designation for the indication of Squamous Cell Carcinoma of the skin and oral cavity without curative standard of care, and preclinical studies support evaluation across various cancer indications (skin, pancreas, breast and GBM, among others).

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– The transaction represents an implied pro forma equity value of approximately $1 billion and is expected to provide up to $367 million in gross proceeds, including up to $275 million of cash held in the trust account of Healthcare Capital Corp. (Nasdaq: HCCC) and a $92 million PIPE.

– The $92 million fully-committed PIPE is anchored by a combination of Healthcare-focused financial and strategic investors including Yozma Investment Co. (part of Yozma Group Korea), Grand Decade Developments (an affiliate of China Grand Pharmaceutical and Healthcare Holdings), as well as other leading technology investors including OurCrowd, Regah Ventures and the co-founders of Apax Partners, Alan Patricof and Sir Ronald Cohen. Medison Group, an early supporter of Alpha Tau and global pharma company that provides access to highly innovative therapies to patients in international markets, is also an investor in the PIPE.

– After giving effect to the transaction (and assuming no redemptions by public shareholders), Alpha Tau is expected to have approximately $362 million of cash on the balance sheet.

– Net proceeds are to be used for further expansion of Alpha Tau’s clinical strategy including the pursuit of FDA marketing authorization, a broad array of R&D activities, expanding manufacturing capacity and preparing for commercialization, and are expected to provide cash runway at least into 2024.

– All Alpha Tau shareholders will retain 100% of their equity holdings in the public company.

– Alpha Tau will continue to be led by its current management team, and upon closing, it is expected that HCC Chairman Dr. David M. Milch will be appointed to the Alpha Tau Board of Directors.

– The proposed business combination is expected to be completed by the end of 2021, upon which Alpha Tau is expected to be listed on Nasdaq.

JERUSALEM and WILMINGTON, Del., July 8, 2021 /PRNewswire/ — Alpha Tau Medical Limited ("Alpha Tau"), the developer of the pioneering alpha-radiation cancer therapy Alpha DaRT, and Healthcare Capital Corp. ("HCC") (Nasdaq: HCCC), a special purpose acquisition company, reported they have entered into a definitive business combination agreement (the "Business Combination"). Upon closing of the Business Combination, Alpha Tau is expected to be listed on the Nasdaq.

Alpha Tau’s proprietary Alpha DaRT (Diffusing Alpha-emitters Radiation Therapy) enables highly potent and conformal alpha-irradiation of solid tumors through the intra-tumoral insertion of radium-224 impregnated sources mainly affecting the tumor, sparing the healthy tissue around it. In the company’s first-in-human clinical trial for Squamous Cell Carcinoma ("SCC") tumors of the skin & oral cavity exhibited 100% overall response rate and approximately 78% complete response rate. In June 2021, Alpha Tau received FDA Breakthrough Device Designation for the use of Alpha DaRT in the treatment of SCC of the skin and oral cavity without curative standard of care.

Alpha Tau has developed a robust clinical trial strategy with leading global centers, including its flagship US multi-center feasibility study currently ongoing, led at Memorial Sloan Kettering Cancer Center in New York, which recently enrolled its first patient.

A group of Healthcare-focused financial and strategic investors have committed to participate in the transaction through a fully committed ordinary share PIPE of approximately $92 million at $10.00 per share. Investors in the PIPE include Yozma Investment Co. (part of Yozma Group Korea) and Grand Decade Developments (an affiliate of China Grand Pharmaceutical and Healthcare Holdings) as well as other leading technology investors including OurCrowd, Regah Ventures and the co-founders of Apax Partners, Alan Patricof and Sir Ronald Cohen. Medison Group, an early supporter of Alpha Tau and global pharma company that provides access to highly innovative therapies to patients in international markets, is also an investor in the PIPE.

"Following the recent enrollment of the first patient in our flagship US feasibility study and receipt of FDA Breakthrough Device Designation, this transaction represents another significant milestone on Alpha Tau’s journey to transform the treatment of solid tumors through the precision delivery of alpha radiation. We are grateful to the outstanding team at HCC, whose cadre of experienced and well-regarded professionals have provided superb execution and continued support for Alpha Tau, and we are excited for Dr. David M. Milch to join as our newest member of the Board of Directors upon the closing of the business combination. We thank our investors, both new joiners as well as those who have supported us for years, who continue to demonstrate their faith in the company and its leadership," said Uzi Sofer, CEO and Chairman of Alpha Tau.

"The completion of this transaction will allow the company to realize its vision and implement the clinical development plans and construction of our manufacturing plants around the world, in order to bring hope to millions of patients around the world."

"This transaction ensures that we are well capitalized to accelerate our ambitious plans across multiple fronts," said Raphi Levy, CFO of Alpha Tau. "We look forward to delivering continued clinical momentum and hope for patients as we evolve into a public company."

"We are excited about Alpha Tau’s unique therapy, which has generated a response observed across a wide array of solid tumors in pre-clinical studies, with minimal side effects, positioning it to potentially become a vital weapon in the battle against cancer," said Dr. David M. Milch. "After evaluating many opportunities in the healthcare industry, we believe that Alpha Tau stands out as the best choice for a business combination due to its proprietary technology, rapid clinical and product development and easy to administer treatment solution for the great number of cancer patients worldwide."

"It was a pleasure to work with the team at HCC as their due diligence advisor following my departure as Commissioner of the FDA in January 2021," said Dr. Stephen M. Hahn. "My background as a medical and radiation oncologist helped me immediately appreciate the potential of Alpha Tau’s therapy in providing a solution for a potentially significant number of patients, including those with untreatable or difficult to treat tumors, whether alone or in combination with other therapies such as immunotherapies. I would expect the product to be well received by the clinical community because of the potential applications, modest side effect profile, and demonstrated potency of the Alpha DaRT"

Proceeds of the business combination and the PIPE will be primarily used to:

advance ongoing, and launch, new clinical trials;

continue existing, and initiate additional, clinical and research collaborations;

develop and expand global manufacturing capacity;

develop KOL centers of excellence; and

prepare for commercialization efforts.

Key Transaction Terms

The Business Combination values Alpha Tau at an implied pre-money equity value of $600 million, and is expected to add approximately $337 million of cash to its balance sheet upon closing, inclusive of $275 million in HCC’s trust (assuming no redemptions by public shareholders) and $92 million in PIPE proceeds, net of transaction expenses.

All existing Alpha Tau shareholders will retain 100% of their current equity holdings and are expected to hold approximately 59% of the pro forma company immediately following the closing. Following the closing of the business combination, Alpha Tau is expected to be listed on the Nasdaq.

The Business Combination was unanimously approved by each of Alpha Tau’s and HCC’s Boards of Directors, and HCC Chairman Dr. David M. Milch is expected to join the Board of Directors after closing. The transaction is expected to be completed by the end of 2021, and is subject to obtaining necessary regulatory approvals, the fulfillment of customary closing conditions, as well as the approval of both Alpha Tau’s and HCC’s shareholders.

Additional information about the proposed business combination, including a copy of the definitive agreement and investor presentation, will be provided in a Current Report on Form 8-K to be filed by HCC with the Securities and Exchange Commission and available at www.sec.gov.

Advisors

Citigroup is acting as financial advisor to Alpha Tau. Citigroup, Piper Sandler, and Cantor Fitzgerald are acting as joint placement agents on the PIPE. Cantor Fitzgerald is acting as a capital markets advisor to HCC. Value Base M&A Ltd. is also acting as financial advisor on the transaction.

Latham & Watkins LLP and Meitar | Law Offices are acting as legal advisors to Alpha Tau. Ellenoff Grossman & Schole LLP and FBC & Co. are acting as legal advisors to HCC. Winston & Strawn LLP is acting as legal advisor to the placement agents.

Management Presentation

A link to a presentation by management of Alpha Tau and HCC discussing the business and the proposed transaction can be found at www.netroadshow.com/nrs/home/#!/?show=d422ce03

The investor presentation is being filed by Alpha Tau and HCC with the Securities and Exchange Commission ("SEC") and will be available on the SEC’s website at www.sec.gov.

OSE Immunotherapeutics Receives a €10 Million Payment Corresponding to the First Tranche of the Financing Granted by the European Investment Bank

On July 9, 2021 OSE Immunotherapeutics reported a €10 million payment corresponding to the first tranche of the financing granted by the European Investment Bank (EIB) (Press release, OSE Immunotherapeutics, JUL 9, 2021, View Source [SID1234646979]). The finance contract was signed on February 12, 2021.

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The finance contract allows the Company to borrow up to €25 million. The second and third tranches, respectively of €10 million and €5 million, may be drawn at the hand of the Company, subject to the achievement of specific clinical steps.

This type of financing, granted by the EIB and benefiting from a guarantee from the European Commission within the framework of the European Fund for Strategic Investments (known as the "Juncker Plan"), aims to support development research and innovation projects developed by companies with high growth potential.

This first tranche will carry a fixed interest of 5% per year paid annually, with a maturity of five years.

The first tranche is associated to the issuance of warrants to the EIB giving right, in the event of exercise, to the subscription of 850,000 shares of the Company (i.e. 4.44% of the share capital on an undiluted basis). Warrants are not the subject of an application for admission to trading on any market.

The subscription price is €0.01 per warrant, i.e, €8,500.
In order to limit the dilutive impact over time, and except in the event of the occurrence of an early exercise event (notably a change of control, including the loss of a significant holding by the current management shareholders, or other events of default, including a significant change in the current governance not approved by the EIB), the warrants will only be exercisable from 9 July 2026, i.e. five years from the drawdown of the relevant tranche and at the latest at the end of a period of twelve years following their issue (i.e. 9 July 2033).

The subscription price for the new shares upon exercise of the warrants was set at 10.59 euros per share, i.e. a discount of 2.5% compared to the volume-weighted average of the three trading days preceding the pricing.

In accordance with the warrant agreement, the EIB has an anti-dilution clause allowing it to benefit from additional warrants, in the event of a capital increase of the Company at a price less than €20 per share, after application of a deductible on the first 1,500,000 shares to be issued. In such a case, the Company would have to allocate additional warrants to the EIB allowing it to remain at a potential capital level of 4.44% (corresponding to its theoretical holding percentage post-allocation and exercise of the warrants subscribed in the context of the first tranche of funding).

The shares to be issued upon exercise of the warrants will be subject to an application for admission to trading on Euronext Paris. On the basis of 850,000 new Company’s shares issued upon exercise of all the warrants at a price of 10.59 euros per new share, the gross proceeds of the issue, issue premium included, will amount to 9,001,500 euros.

On 9 July 2026, the EIB has the option to ask the Company to buy back its warrants at market value (less the exercise price of the warrants) up to a maximum of EUR 15 million, provided that the Company retains a cash level of at least EUR 10 million. Otherwise, the EIB’s put option will be exercised on a number of warrants allowing the Company to maintain a cash level of 10 million euros. This put option also applies in the event of a change of control, understood as the holding of more than 33% of the capital or the taking of control by a third party (other than the current key managers). The Company may substitute an existing shareholder or a third party to buy back these warrants at market value. The Company has a call option allowing it to buy back the EIB warrants at market value (less the exercise price of the warrants) in the event of a public offer by a third party resulting in the exit of the management shareholders, for a period of one month following such exit. The Company also has a right of first refusal allowing it to buy back the EIB’s warrants if the latter wishes to sell them to a third party.

Tempest to Participate in William Blair 2021 Biotech Focus Conference

On July 9, 2021 Tempest Therapeutics, Inc. (Nasdaq: TPST), a clinical-stage oncology company developing potentially first-in-class therapeutics that combine both targeted and immune-mediated mechanisms, reported that Sam Whiting, M.D., Ph.D., chief medical officer, will participate in a webcast panel titled "Developing Therapies for the Next Immuno-Oncology Targets" at the William Blair 2021 Biotech Focus Conference on Wednesday, July 14, 2021 at 2:10 p.m. ET (Press release, Tempest Therapeutics, JUL 9, 2021, View Source [SID1234585167]).

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To access the live or archived recording of the discussion, please visit the investor section of the Tempest website at View Source