On November 8, 2021 iOnctura SA, a clinical stage oncology company targeting core resistance and relapse mechanisms at the tumor-stroma-immune interface, reported it has fully enrolled the metastatic uveal melanoma expansion cohort of the DIONE-01 study evaluating iOnctura’s lead compound, the selective PI3Kδ inhibitor IOA-244 (Press release, iOnctura, NOV 8, 2021, View Source [SID1234640243]).

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The DIONE-01 study entitled "A Study to Assess a PI3Kδ Inhibitor (IOA-244) in Patients with Metastatic Cancers" (NCT04328844) consists of two parts, A and B. In Part A, now complete, the objective was to determine the safety, tolerability, and dosage of IOA-244 in cancer patients to determine the predicted biologically effective dose range. Safety, PK and PD data from Part A will be presented as a poster (#405) at ESMO (Free ESMO Whitepaper) IO in Geneva between December 8-11, 2021.

Part B of the DIONE-01 study consists of expansion cohorts of patients with different tumor types, including patients with metastatic uveal melanoma. It will include the assessment of whether IOA-244 can increase the anti-tumor immune response in patients both as monotherapy and in combination with pemetrexed/cisplatin and an immune checkpoint inhibitor. The study will enroll up to 182 patients with uveal melanoma, cutaneous melanoma, NSCLC, mesothelioma, myelofibrosis, and NHL.

Within Part B, up to 26 patients with metastatic uveal melanoma will be recruited to determine the monotherapy activity of IOA-244. Patients with metastatic uveal melanoma currently have no approved treatment options. Positive outcome from this part of the trial is expected to support transition to subsequent registration studies for metastatic uveal melanoma. Interim data is expected in Q2 2022 with final top-line data scheduled for Q4 2022.

"iOnctura is entering a highly exciting phase as it progresses two tumor-stroma-immune interface targeting programs through clinical development. IOA-244 continues to demonstrate an unprecedented clinical profile among PI3Kδ inhibitors," said Catherine Pickering, CEO of iOnctura. "iOnctura is moving rapidly in the use of IOA-244 to treat a range of solid tumor types including metastatic uveal melanoma, an underserved cancer with no currently approved drug treatments and poor patient outcomes. We look forward to releasing early data from our preclinical and clinical evaluations of this exceptional molecule at ESMO (Free ESMO Whitepaper) IO."

Contacts

iOnctura
Catherine Pickering
Chief Executive Officer
T : +41 79 952 72 52
E: [email protected]

Press Relations
Jeremy Nieckowski
LifeSci Advisors
T: +41 79 699 97 27
E: [email protected]
iOnctura SA is clinical stage oncology company targeting core resistance and relapse mechanisms at the tumor-stroma-immune interface. iOnctura’s best-in-class drug development programs combine immune-mediated and direct anti-tumor activity to deliver molecules with superior clinical efficacy and safety in oncology. Its lead program, IOA-244 is the only semi-allosteric PI3Kδ specific, orally dosed, small molecule inhibitor that is being developed in solid and hematologic malignancies to address tumor and stroma induced immune suppression. IOA-244 is currently in a Phase 1 study which will support transition to subsequent registration studies. iOnctura’s second program, IOA-289, is an oral small molecule that inhibits the cross-talk between the tumor and its stroma and is in a Phase 1 study. iOnctura is backed by blue chip investors including M Ventures, Inkef Capital, VI Partners, Schroders Capital, and 3B Future Health Fund. For more information, please visit www.ionctura.com

IOA-244 is a PI3Kδ specific, orally dosed, small molecule inhibitor that overcomes tumor and stroma induced immune suppression. Its unique chemistry, semi allosteric binding mode and mechanism of action contribute to its unprecedented clinical profile. IOA-244 is currently in the cohort expansion phase of the DIONE-01 trial, a two-part, first-in-human dose study evaluating IOA-244 in solid tumors and hematologic malignancies and as a combination partner for conventional and immune-therapies.

Uveal melanoma (UM) is a rare malignancy arising within the uveal tract of the eye. There are approximately 7,000 newly diagnosed cases of uveal melanoma each year (around 2,000 in the United States). Over 50% of patients will progress to metastatic disease. Median overall survival is approximately 1 year for metastatic uveal melanoma and there are no approved therapies.

On November 8, 2021 RedHill Biopharma Ltd. (Nasdaq: RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company, reported that it has entered into a strategic agreement with Kukbo Co. Ltd. (Kospi: 001140) ("Kukbo"), a South Korean corporation, for the sale of RedHill’s American Depositary Shares ("ADSs") in a private placement of up to $10 million at a 20% premium to the prior 30 trading days’ volume weighted average price ("VWAP") (Press release, RedHill Biopharma, NOV 8, 2021, View Source [SID1234595344]).

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Kukbo’s strategic investment in RedHill is to be made in two tranches, with the first tranche of $5 million already paid and the second tranche of $5 million to follow within six months, subject to satisfaction of certain conditions. As part of the first tranche, RedHill is to issue 827,586 ADSs at a purchase price of $6.04, representing a 20% premium based on the VWAP of RedHill’s ADS on NASDAQ over the 30 trading days ending on the effective date. All ADSs are to be issued with a 180-day transfer restriction.

In addition, under the terms of the agreement, RedHill has agreed to grant Kukbo a right of first offer, for a period of six months, for a license with respect to one or more of RedHill’s late-stage clinical assets, opaganib, RHB-107 (upamostat)1 and Talicia, for one or more of the territories of South Korea, Japan, Indonesia, Vietnam, Thailand and Malaysia. Kukbo has the right to elect not to purchase the ADSs in the second tranche if no such license agreement is executed within six months of the closing of the first tranche.

Dror Ben-Asher, RedHill’s CEO said: "We are rapidly advancing with opaganib’s COVID-19 data package submissions to regulators in several territories including the U.S., EU and others, ahead of planned regulatory advice. We are pleased with the addition of Kukbo as a committed strategic investor and look forward to evaluating opportunities for opaganib, RHB-107 and Talicia in South Korea and other territories in Asia where large unmet medical needs exist."

"As Kukbo proceeds in its planned strategic expansion into healthcare, we believe that RedHill’s opaganib, RHB-107 and Talicia, if approved, hold substantial promise in South Korea and other Asian countries and are eager to leverage our local expertise and network in those territories," said Hyun Ha, Kukbo’s CEO.

Nexpedia Holdings Co., Ltd. and Network 1 Financial Securities, Inc. facilitated the introduction between the parties.

The securities to be sold in the private placement have not been registered under the Securities Act of 1933, as amended (the "Securities Act"), or any state or other applicable jurisdiction’s securities laws, and may not be offered or sold in the United States absent registration or an applicable exemption from the registration requirements of the Securities Act and applicable state or other jurisdictions’ securities laws.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any offer, solicitation, or sale of these securities in any jurisdiction in which such offer, solicitation or sale would be unlawful.

On November 8, 2021BioXcel Therapeutics reported that it raised $60 million in an initial public offering a few years back, it said it would pour part of the proceeds into developing talabostat, a drug that failed a phase 3 trial in pancreatic cancer in 2007 (Press release, BioXcel Therapeutics, NOV 8, 2021, View Source [SID1234595336]). Now, BioXcel, along with collaborators at Georgetown University, has preclinical data suggesting the drug may boost the benefits of immunotherapy in this tough-to-treat cancer.

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Georgetown researchers tested talabostat (also known as BXCL701) alone and alongside a treatment that inhibits the immune checkpoint PD-1 in mouse models of pancreatic cancer. Both treatments slowed tumor growth, and the combination significantly increased the recruitment of cancer-fighting immune cells, the researchers reported in the Journal for ImmunoTherapy of Cancer.

Talabostat works by inhibiting the protein dipeptidyl peptidase (DPP). Knowing that earlier studies had suggested the drug might improve immunotherapy, the Georgetown researchers wanted to see what would happen if they combined it with PD-1 inhibition. Checkpoint blockade has worked in many cancer types but has so far not panned out in pancreatic cancer.

They discovered that talabostat ramped up the infiltration of T cells and natural killer (NK) cells into the pancreatic tumor environment. Combining the drug with anti-PD-1 therapy not only slowed tumor growth and boosted immune activity, it also created "immune memory" in 10 out of 13 mice that had been cured by the initial therapy, allowing them to clear some tumors after they were re-exposed to pancreatic cancer months later.

The researchers believe the key to the combination’s effectiveness rested in the recruitment of NK cells, which combat cancer in two ways: They kill cancer cells directly, and they release "signaling molecules" that regulate other aspects of the immune system in ways that control tumor growth, they explained in a statement.

To back up their hunch, they studied real-world data in the National Institutes of Health’s Cancer Genome Atlas and found that increased levels of NK cells in human pancreatic tumors correlated with longer survival, the team reported.

RELATED: AACR (Free AACR Whitepaper): Attacking pancreatic cancer by thwarting its survival strategies

NK cells are of great interest to several research groups and biotechs that are searching for new approaches to treating solid tumors. Fate Therapeutics, for example, is developing an NK cell therapy that in preclinical studies killed cancer cells—including pancreatic tumor cells—when combined with anti-PD-1 therapy. The investigational product, FT500, is now in phase 1 testing in advanced solid tumors.

Other combinations designed to boost the immune response are under investigation in pancreatic cancer. Last year at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) conference, a University of Minnesota team reported that combining a PD-L1 inhibitor with a CD40 blocker in mouse models of pancreatic cancer eliminated tumors in 60% of the animals. Apexigen is testing its CD40-targeted drug in combination with Bristol Myers Squibb’s PD-1 blocker Opdivo and other therapies in pancreatic cancer and reported survival benefits over the standard of care earlier this year.

As for BioXcel, it is currently testing talabostat in combination with Merck’s blockbuster PD-1 inhibitor Keytruda in metastatic castration-resistant prostate cancer and some tumors that are resistant to immune checkpoint inhibitors.

The Georgetown researchers said they’re planning to conduct additional animal trials to better understand the mechanism of action of the talabostat-anti-PD-1 combination in pancreatic tumors. From there, they hope to design a clinical trial, they said.

On November 8, 2021 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, and Blackstone Life Sciences reported that the two companies have entered into a strategic collaboration and financing agreement under which funds managed by Blackstone (NYSE: BX) will provide up to $250 million in equity and product financing to support Autolus’ advancement of its CD19 CAR T cell investigational therapy product candidate, obecabtagene autoleucel (obe-cel), as well as next generation product therapies of obe-cel in B-cell malignancies (Press release, Blackstone Life Sciences, NOV 8, 2021, View Source [SID1234595327]).

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As part of this $250 million transaction, Blackstone is committing to invest $150 million in product financing to support obe-cel development and commercialization, with $50 million payable upon closing of the transaction and the remainder payable based on certain development and regulatory achievements. Blackstone has also agreed to purchase $100 million of Autolus’ American Depositary Shares (ADS) in a private placement, which is subject to customary closing conditions. In connection with the collaboration, Blackstone received the right to nominate a member to Autolus’ board of directors.

The transaction continues Blackstone’s commitment to the UK economy which has seen the firm invest more than $18 billion across 44 investments headquartered in UK. These investments support more than 27,000 direct jobs and help make Blackstone the UK’s biggest foreign investor over the past 10 years.

"Autolus is a world-class company with an innovative platform and the potential to deliver best-in-class, lifesaving treatments to patients suffering from cancer," said Dr. Nicholas Galakatos, Global Head of Blackstone Life Sciences. "Our investment in these next generation cell therapies exemplify our conviction in the quality and promise of the life sciences sector in the UK. We look forward to building on this investment in the years to come."

"We welcome Blackstone Life Sciences to join our drive to change the outlook for leukemia and lymphoma patients, notably those with acute lymphoblastic leukemia. Blackstone’s investment and expertise will support the development and preparation for commercialization of obe-cel and put the program and the Company on a strong financial footing as we are approaching the read-out from the potentially pivotal FELIX clinical trial during the course of 2022," said Dr. Christian Itin, Chief Executive Officer of Autolus.

"We are excited to collaborate with Autolus in support of their innovative platform pursuing safer, more durable, therapies with the potential to be lifesaving options for patients with ALL and beyond. We see a significant opportunity to improve the outlook for cancer patients who are facing a devastating course of their disease," said Nicholas Simon, Senior Managing Director of Blackstone Life Sciences. "This investment continues to build on our conviction in not just innovative cell and gene therapies, but also supporting innovation in the United Kingdom and Europe broadly."

UK Science Minister George Freeman said: "This is another vote of confidence in the quality of life science in the UK, reinforcing our reputation as a world leader in discovering new cures for currently untreatable diseases like Autolus’ T cell therapy drugs for leukemia. Big investments like these give real hope to those suffering from diseases like leukemia – and create high skill jobs & opportunities in the development and manufacturing of treatments to help develop and boost our life science clusters all around the UK."

Autolus recently announced plans to build a dedicated manufacturing facility in Stevenage, UK to help secure global commercial launch capacity for obe-cel with a 70,000 square foot building. The ground-breaking ceremony for this new facility is due to be held today, with building works commencing imminently.

Moelis & Company LLC acted as financial advisor. Cooley LLP and Cooley (UK) LLP acted as legal advisor to Autolus, and Goodwin Procter LLP acted as legal advisor to Blackstone.

About the Transaction

The strategic financing collaboration by Autolus and Blackstone Life Sciences is expected to support the development and preparation for commercialization of Autolus’ product candidate, obe-cel. As part of this $250 million transaction, Blackstone is committing to invest an aggregate of $150 million in product financing to support Autolus’ development and potential commercialization of obe-cel, with $50 million payable upon closing of the transaction and the remainder (up to $100 million) payable based on certain development and regulatory achievements. In return for this strategic investment, Autolus has agreed to pay Blackstone a capped single digit royalty plus milestone payments based on net sales of obe‐cel. In addition, Blackstone will receive a warrant to purchase up to $24 million worth of Autolus ADSs at an exercise price premium to market. Blackstone has also agreed to make a $100 million equity investment in Autolus which is expected to close on or about November 12, 2021, subject to customary closing conditions. In connection with the collaboration, Blackstone received the right to nominate a member to Autolus’ board of directors.

On November 8, 2021 Delcath Systems, Inc. (Nasdaq: DCTH ), an interventional oncology company focused on the treatment of rare primary and metastatic cancers of the liver, reported it will participate in an upcoming virtual investor conference (Press release, Delcath Systems, NOV 8, 2021, View Source [SID1234595227]):

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Canaccord Virtual MedTech, Diagnostics and Digital Health & Services Forum
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