On January 6, 2022 Plus Therapeutics, Inc. (Nasdaq: PSTV) (the "Company"), a clinical-stage pharmaceutical company developing innovative, targeted radiotherapeutics for rare and difficult-to-treat cancers, reported that it has entered into an agreement with The University of Texas Health Science Center at San Antonio (also referred to as UT Health San Antonio) for a worldwide exclusive license to develop and commercialize novel interventional therapeutics for cancer (Press release, Cytori Therapeutics, JAN 6, 2022, View Source [SID1234598315]).

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"The future of cancer therapy is precise targeting of tumors with the most potent cancer-killing agents while minimizing damage to normal tissues," stated Marc H. Hedrick, M.D., President and Chief Executive Officer of Plus Therapeutics. "Not only does this important transaction further expand our existing Rhenium NanoLiposome technology, but it also helps realize this future. With this technology, we can target almost any solid organ tumor in the body using standard interventional means to leverage the breadth of the human vascular system and deliver a resorbable biomaterial embolic technology coupled with a highly potent radiotherapeutic isotope."

The licensed patents include composition of matter patents for biodegradable alginate microspheres (BAM) containing nanoliposomes loaded with imaging and/or therapeutic payloads. Therapeutic payloads may include radiotherapeutics, chemotherapeutics or thermotherapeutics. The BAM technology is delivered into the vascular system via standard interventional vascular catheters that are placed precisely in the vessels feeding tumors. Once injected, BAM blocks all blood flow to the tumors and simultaneously delivers very high doses of cytotoxic compounds for an extended time. Many days later, the BAM resorbs and are physiologically metabolized and excreted from the body.

"Embolization technology for many types of tumors, including liver cancer, has been used with promising results for over two decades, but substantial limitations remain, and no meaningful recent technological innovations have been made," said William Phillips, M.D., Professor of Nuclear Medicine at UT Health San Antonio. "The leading radioembolization therapies available today incorporate Yttrium-90 glass/resin microspheres which have poor imaging characteristics, require long lead times, are permanently implanted and may expose the marrow to high levels of radiation. Rhenium-188 NanoLiposome Biodegradable Alginate Microsphere (188RNL-BAM) is a next generation, fully resorbable technology that solves many of the problems of existing technology. Our team at UT Health San Antonio intends to support Plus Therapeutics in bringing this technology rapidly to market."

The financial terms of the exclusive license agreement are primarily success-based with milestone and royalty payments contingent on achieving key clinical, regulatory and sales milestones.

The Company will initially focus on developing 188RNL-BAM as a next-generation radioembolization therapy for liver cancer, in which BAM blocks the hepatic artery segments that supply blood to the malignant tumor while also providing 188RNL radiotherapy by directly irradiating the tumor.

"This transaction is the next step in our plan to expand our pipeline using precision, targeted radiotherapeutics," said Norman LaFrance, M.D., Chief Medical Officer of Plus Therapeutics. "Next steps are to complete and compile the promising preclinical work performed thus far and prepare for an IND submission in 2022 for the treatment of liver cancer."

Liver cancer is a rare disease with an increasing annual incidence and 5-year overall survival of only 20%1. The global opportunity for localized embolization, chemoembolization, and radioembolization therapies for primary (hepatocellular carcinoma) and secondary (typically metastatic colorectal cancer, for example) liver cancer is $1.3 billion2.

The initial inventions and work behind the licensed patents and technologies were developed and led by William Phillips M.D., Professor of Nuclear Medicine, Ryan Bitar, M.D., and their team at UT Health San Antonio. The 188RNL-BAM technology incorporates Rhenium-188, or 188Re, a very attractive isotope for use in radiotherapeutic embolization owing to its emission of a high energy electron (beta particle) with a half-life of 16.9 hours and a path length of 3.1 mm. 188Re emits gamma energy that permits high quality, real-time imaging of the BAM construct delivery localization and confirmation. 188RNL-BAM is straightforward and cost-effective to manufacture for on-demand availability for therapeutic applications and is versatile and can be precisely composed and manufactured to a specific size allowing optimal arterial embolization to block blood flow in most vascular beds while simultaneously delivering its isotopic payload to the tumor. BAMs are not permanent like other technology and degrade over time, allowing restoration of blood flow, decreasing radiation resistance, and allowing safer physiological and safe clearance of 188Re through the kidneys, which avoids bone marrow toxicity.

1American Cancer Society; 2Internal estimate

On January 6, 2022 Affimed N.V. (Nasdaq: AFMD), a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer, reported that it has completed enrollment in the REDIRECT study and provided a business update (Press release, Affimed, JAN 6, 2022, View Source [SID1234598314]).

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REDIRECT, also known as AFM13-202 (NCT04101331), is a registration-directed phase 2 open-label, multicenter, global study investigating the efficacy and safety of AFM13 monotherapy in patients with relapsed or refractory CD30-positive peripheral T-cell lymphoma (PTCL). Affimed expects to report topline data from the REDIRECT study in the second half of 2022.

"Completing the enrollment in the registration directed trial of AFM13, our lead innate cell engager, is an important milestone for us and reflects our ability to progress and advance our clinical pipeline. The high response rates reported in December 2021 from our combination study with natural killer cells in Hodgkin Lymphoma represent a marked expansion of the business opportunity of AFM13. We are looking forward to solidifying the opportunity for AFM13 when we report additional data this year," said Dr. Adi Hoess, Chief Executive Officer of Affimed. "Data generated from multiple AFM13 trials provide us with confidence in the development strategy for AFM24 and AFM28, for which we expect to provide additional updates during 2022."

The REDIRECT trial protocol, in addition to the registration relevant cohorts A and B in PTCL, includes an arm to investigate AFM13 therapy in patients with Transformed Mycosis Fungoides (TMF), which is exploratory and not relevant to the potential consideration for accelerated

approval. As previously announced, recruitment of TMF patients was paused due to the COVID-19 pandemic. At this time, Affimed has decided not to pursue the investigation of AFM13 therapy in patients with TMF due to the continuing impact of the COVID-19 pandemic and the completion of enrollment of the registration-directed portion of the trial.

Update on Other Programs

AFM13 (CD30/CD16A ICE)

The United States Food and Drug Administration (FDA) has approved a proposed amendment to the AFM13-104 trial protocol to increase the patient population treated at the recommended phase 2 dose (RP2D) to 40 CD30-positive lymphoma patients, including both Hodgkin Lymphoma (HL) patients and non-Hodgkin Lymphoma (NHL) patients, and allow for the treatment of patients with more than the two cycles of therapy, at the investigator’s discretion. With the approval of the protocol amendment, The University of Texas MD Anderson Cancer Center (MDACC) has initiated enrollment of patients into the phase 2 portion of the trial, triggering an undisclosed milestone payment to MDACC which Affimed expects to make during the first quarter of 2022.

AFM13-104 is an investigator sponsored trial (IST) at MDACC investigating the treatment of CD30-positive lymphoma patients with cbNK cells, pre-complexed with AFM13. In December 2021, Affimed reported updated data from the trial, including a 100% objective response rate after a single cycle of treatment for the 13 patients treated at the RP2D of 1×108 cbNK cells precomplexed with AFM13 followed by 3 weekly infusions of AFM13. All three patients treated at the RP2D with at least 6 months of follow-up remained in complete response as of the cutoff date.

AFM24 (EGFR/CD16A ICE)

During the fourth quarter of 2021, Affimed announced that it had identified the RP2D for AFM24 monotherapy of 480 mg weekly in patients with EGFR-expressing solid tumors. With the achievement of this milestone, Affimed has now embarked on a broad development strategy for AFM24, which includes the initiation of three studies investigating various EGFR-expressing solid tumor indications.

Affimed has initiated enrollment in the expansion phase of the monotherapy AFM24 trial at the RP2D. The trial includes patients with renal cell carcinoma (clear cell), non-small cell lung cancer (EGFR-mutant) and colorectal cancer.

Affimed also initiated enrollment in two separate phase 1/2a combination studies. The first is investigating the combination of AFM24 with SNK01 (ex vivo expanded and activated autologous NK cell therapy from NKGen Biotech) to treat patients with non-small cell lung cancer (NSCLC, EGFR-wildtype), squamous cell carcinoma of the head and neck, and colorectal cancer. The second study will investigate the combination of AFM24 with Roche’s atezolizumab, an anti-PD-L1 checkpoint inhibitor to treat patients with non-small cell lung cancer (EGFR-wildtype), gastric and gastroesophageal junction adenocarcinoma and pancreatic/hepatocellular/biliary tract cancer.

Affimed expects to report data updates from the AFM24 trials during 2022.

AFM28 (CD123/CD16A ICE)

AFM28 is currently being prepared for clinical evaluation with an IND filing planned for the first half of 2022 and a first in human study is planned to start in second half of 2022. Initial preclinical data for AFM28 was presented at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (ASH) (Free ASH Whitepaper) in December 2021, demonstrating antibody-dependent cell-mediated cytotoxicity (ADCC) even at low CD123 expression which was more pronounced compared to conventional anti-CD123 antibodies. In addition, AFM28 showed a 100-fold more potent NK cell activation in an ex vivo analysis, compared to Fc-enhanced IgG1 antibodies. Further, AFM28 was well tolerated and showed pharmacodynamic activity in cynomolgus monkeys.

Preliminary Cash Balance and Cash Runway Guidance

As of December 31, 2021, Affimed’s preliminary unaudited cash and cash equivalents were approximately €197 million. The cash balance includes €7.4 million of net proceeds received from the second tranche of Affimed’s loan agreement with Silicon Valley Bank, which was drawn in December 2021. Based on its current operating plan and assumptions, Affimed anticipates that its cash and cash equivalents will support operations into the second half of 2023.

On January 6, 2022 Odyssey Therapeutics, a biotechnology company pioneering next generation precision immunomodulators and oncology medicines, reported that it has acquired Rahko, a leading quantum machine learning company, adding powerful new tools to Odyssey’s discovery platform to enable faster and more efficient drug discovery ((Press release, Odyssey Therapeutics, JAN 6, 2022, View Source [SID1234598312]).

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"This acquisition gives Odyssey the opportunity to pair artificial intelligence and physics-based methods with a team of master drug-hunters, a combination that is critical to elevating precision medicine and redefining what’s possible in drug development," said Gary D. Glick, Ph.D., Founder and Chief Executive Officer of Odyssey Therapeutics. "Rahko’s powerful platform will play a direct role in identifying the best leads for our targets with unprecedented speed and accuracy, assisting with our efforts to address the undruggable genome with the goal of delivering transformational impact for patients with inflammatory diseases and cancer in record time."

Rahko was founded in 2018 by Leonard Wossnig, Ph.D., Edward Grant, Ph.D., Miriam Cha, and Ian Horobin, with financing from Balderton Capital. Rahko has built a quantum drug discovery platform that brings together three key technologies—computational chemistry, machine learning, and quantum computing—to drive a better understanding of the behavior of drugs. The quantum machine learning models in Rahko’s platform combine physics and machine learning, enabling faster and better chemical simulations, systematic limitation of prediction errors, and reduction of the amount of data required to create models. The dynamics of these proteins are explored using physics-based simulation methods that uncover novel binding sites such as cryptic pockets. This information is combined with structure-based generative machine learning methods to generate novel molecular candidates to rapidly start programs with the best possible chemistry. Odyssey is also combining Rahko’s quantum machine learning methods with functional genomics and other omics data to identify novel targets.

"Since Rahko’s founding, we have focused on removing key bottlenecks in drug discovery using quantum machine learning descriptors and models for best-in-class lead identification and optimization of drug candidates," said Leonard Wossnig, Ph.D., Co-Founder and former Chief Executive Officer of Rahko, now Vice President of artificial intelligence at Odyssey Therapeutics. "The current renaissance in medicinal chemistry, new drug discovery technologies, and an expanded understanding of the drivers of immune dysfunction and cancer represent precisely the kind of unprecedented opportunity our platform was designed to maximize."

Odyssey has developed a strategy to create a portfolio of product candidates that will go beyond the limitations of current medicines and enhance the standard-of-care for patients living with inflammatory diseases and cancer. The company is focused on targets and mechanisms that control validated signaling nodes that drive diseases and will create medicines that achieve optimal product profiles for patients. In addition, Odyssey is applying its highly integrated drug hunting engine and class-leading computational and data sciences platform to challenging, high-value targets that have the potential to revolutionize treatment paradigms, but for which traditional discovery approaches have not succeeded.

In December 2021, Odyssey announced the completion of an oversubscribed $218 million Series A financing led by OrbiMed Advisors and co-led by SR One Capital Management with participation from Foresite Capital, Woodline Partners LP, Logos Capital, HBM Healthcare Investments, Colt Ventures, Creacion Ventures, and other institutional investors.

On January 6, 2022 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") reported that it has entered into a License Agreement granting the exclusive rights for global research, development, manufacture and sale of the investigational anticancer agent H3B-8800 to a subsidiary of Roivant Sciences Ltd. (Nasdaq: ROIV, Headquarters: London, U.K., "Roivant") (Press release, Eisai, JAN 6, 2022, View Source [SID1234598214]). H3B-8800 (Roivant’s Development Code: RVT-2001) is a splicing modulator compound, discovered by Eisai’s U.S. research subsidiary H3 Biomedicine Inc., which is undergoing development as an investigational anticancer agent.

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H3B-8800 is an orally available small molecule modulator of splicing factor 3B subunit 1 (SF3B1), discovered by H3 Biomedicine Inc. Splicing occurs to remove introns that are base sequence of pre-messenger RNA (mRNA), unneeded for protein synthesis, in the process of synthesizing proteins based on the genetic code. Mutations in splicing factor-encoding genes are observed in multiple hematological malignancies and solid tumors. SF3B1 is a particularly frequent gene mutation in splicing factors.1,2 H3B-8800 binds to SF3B1, and demonstrated significant antitumor activity in preclinical models by modulating the disruption of mRNA splicing in cancer.3 Eisai and H3 Biomedicine Inc. are currently conducting a Phase I clinical trial of H3B-8800 in the U.S. and Europe in patients with myelodysplastic syndrome carrying SF3B1 mutations.

Under the terms of the agreement, Eisai will receive a contractual up-front payment, development, and regulatory milestone payments for H3B-8800, and will also receive a certain amount of royalties on sales revenue of H3B-8800 after the launch.

Roivant is a biopharmaceutical company with a unique business model. Roivant builds and launches subsidiaries, called "Vants" which conduct efficient clinical development in diverse therapeutic areas. Eisai believes that this License Agreement with Roivant will lead to the maximization of the value of H3B-8800. Eisai will continue to accelerate its discovery of new medicines based on cutting-edge cancer research, as it seeks to contribute further to addressing the diverse needs of, and increasing the benefits provided to, patients with cancer, their families, and healthcare providers.

On January 5, 2022 Protai, an AI-powered drug discovery startup, reported its emergence from stealth, along with an $8 million seed financing round co-led by Grove Ventures and Pitango HealthTech (Press release, Protai Bio, JAN 5, 2022, View Source [SID1234647409]). The funding will be used to further develop Protai’s platform, accelerate its discovery programs and enhance its partnerships with pharmaceutical companies.

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Despite the significant contribution of genome-level information to the efforts of drug R&D, this information fails to represent the functional layer of the cell reflected and dominated by proteins. This lack of functional understanding of a disease’s molecular mechanisms is one of the main shortcomings of the current drug discovery and development process.

Protai has built an end-to-end AI-based platform that comprehensively maps the course of a disease on the protein level, enhancing the ability to observe cellular function and thereby improving the way new drugs are discovered. This effective approach enables Protai to increase accuracy in drug discovery and improve the development process, substantially saving time and lowering the costs of R&D.

"Protai’s platform is like a unique compass for directing drug discovery," said Eran Seger, CEO and co-founder of Protai. "We are systematically mapping diseases on the protein level to create an entirely new layer of functional information which enables us to identify therapeutic and diagnostic targets to better combat a wide range of complex diseases."

Protai has created the world’s largest and most diverse proteomic database with over 50,000 clinical samples by harmonizing large clinical datasets, as well as healthy samples from various organs and indications. This enables Protai to establish a baseline to then accurately simulate biological functional processes for a variety of diseases and accelerate drug R&D through clinical and preclinical stages.

"Protai is leading a paradigm shift in proteomics based drug discovery by creating a new class of high-quality data that was previously not available to drug researchers and development professionals," said Ittai Harel, General Partner at Pitango Venture Capital. "We are proud to support the founders and the company, as we expect its advanced technology to promote effective novel drug and biomarker development."

"Our investment in Protai highlights Grove Ventures’ increasing commitment to the potential of AI in improving drug discovery and development," said Lior Handelsman, General Partner at Grove Ventures. "We are happy to partner with this exceptional team, and we are positive that Protai will make a huge leap forward in how drug candidates are selected and in how people are treated and cured."