On January 6, 2022 Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading genome editing company focused on developing curative therapies leveraging CRISPR-based technologies, reported its expected milestones and the following strategic priorities for 2022 (Press release, Intellia Therapeutics, JAN 6, 2022, View Source [SID1234598317]):

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Accelerating clinical validation of in vivo pipeline: Further characterize the safety and efficacy of NTLA-2001, including in patients with cardiomyopathy and complete enrollment of the Phase 1 study; establish the initial clinical profile of NTLA-2002 as a single-dose therapy for the treatment of hereditary angioedema (HAE).
Strategic pipeline expansion: Significantly progress in vivo and ex vivo pipeline, including determining the initial safety profile of NTLA-5001 for acute myeloid leukemia (AML), advancing in vivo insertion candidates and nominating multiple new development candidates.
Platform innovation: Broaden the Company’s industry-leading platform through expansion of Intellia’s genome editing, delivery and cell engineering capabilities.
"Unequivocally, 2021 was a landmark year for Intellia. We demonstrated that our proprietary CRISPR-based platform and LNP technology can turn revolutionary science into potentially transformational medicines. Our platform enables us to advance genome editing approaches, which maximizes our ability to target a multitude of life-threatening diseases," said Intellia President and Chief Executive Officer John Leonard, M.D. "As we begin 2022 with great momentum, we are poised to significantly expand our full-spectrum pipeline of potentially curative therapies with the nomination of at least two new in vivo candidates and our first allogeneic development candidate during the year. Importantly, we look forward to sharing additional data from the ongoing study of NTLA-2001 and interim results from the Phase 1/2 study of NTLA-2002, which we expect will further demonstrate the modularity of our genome editing platform."

Anticipated 2022 Milestones:

In Vivo Programs

NTLA-2001 for ATTR amyloidosis: NTLA-2001 is the first investigational CRISPR-based therapy to be systemically delivered to edit genes inside the human body, and has the potential to be the first single-dose treatment for transthyretin (ATTR) amyloidosis. Delivered with the Company’s in vivo lipid nanoparticle (LNP) technology, NTLA-2001 offers the possibility of halting and reversing the disease by driving a deep, lifelong reduction in transthyretin (TTR) protein after a single dose. NTLA-2001 is part of a co-development/co-promotion agreement between Intellia, the lead party for this program, and Regeneron Pharmaceuticals, Inc. (Regeneron).
Today, Intellia announced that the first patient in the cardiomyopathy arm of the Phase 1 study has been dosed with NTLA-2001. This follows the Company’s recent announcement that the United Kingdom Medicines and Healthcare products Regulatory Agency (MHRA) approved a protocol amendment for the Company’s ongoing Phase 1 study of NTLA-2001 to include patients with ATTR amyloidosis with cardiomyopathy (ATTR-CM). The study now includes patients with ATTR-CM enrolled in new dose-escalation and expansion cohorts. The inclusion of the ATTR-CM patient population is in addition to the original Phase 1 study, which continues to evaluate NTLA-2001 in patients with hereditary ATTR amyloidosis with polyneuropathy (ATTRv-PN). Intellia expects to complete enrollment of the Phase 1 study for both ATTRv-PN and ATTR-CM subjects in 2022.
Intellia intends to present additional interim clinical data of NTLA-2001 in ATTRv-PN patients from Part 1, the single-ascending dose portion, and to initiate Part 2, a single-cohort expansion, in the first quarter of 2022. Data to be presented at a company-sponsored event will be from all four ATTRv-PN dose cohorts in Part 1 and include safety and serum TTR knockdown for Cohorts 3 and 4, as well as an early look at durability across all cohorts.
NTLA-2002 for HAE: NTLA-2002 leverages Intellia’s proprietary in vivo LNP delivery technology to knock out the KLKB1 gene in the liver with the potential to permanently reduce total plasma kallikrein protein and activity, a key mediator of HAE. This investigational approach aims to prevent attacks for people living with HAE by providing continuous suppression of plasma kallikrein activity following a single dose and to eliminate the significant treatment burden associated with currently available HAE therapies.
In December 2021, Intellia dosed the first patient in its second clinical study of a CRISPR-based therapeutic candidate evaluating NTLA-2002 for HAE. The first-in-human Phase 1/2 trial is expected to evaluate the safety, tolerability and activity of NTLA-2002 in adults with Type I or Type II HAE, and will continue to leverage insights gained from the development of NTLA-2001.
The Company expects to present interim data from the Phase 1/2 study in the second half of 2022. These results are expected to characterize the emerging safety and activity profile of NTLA-2002 and demonstrate preliminary proof-of-concept.
NTLA-3001 for AATD-associated lung disease: NTLA-3001 is Intellia’s wholly owned CRISPR-mediated in vivo targeted gene insertion development candidate. It is designed with the aim to precisely insert a healthy copy of the SERPINA1 gene, which encodes the alpha-1 antitrypsin (A1AT) protein, with the potential to restore permanent expression of functional A1AT protein to therapeutic levels after a single dose. This approach seeks to address alpha-1 antitrypsin deficiency (AATD)-associated lung disease and eliminate the need for sub-optimal weekly IV infusions of A1AT augmentation therapy or lung transplant in severe cases.
Intellia is conducting Investigational New Drug (IND)-enabling activities for NTLA-3001 with plans to file an IND or IND-equivalent in 2023. The Company also continues to explore additional editing strategies for AATD.
Ex Vivo Programs

NTLA-5001 for AML: NTLA-5001 is an investigational autologous T cell receptor (TCR)-T cell therapy engineered to target the Wilms’ Tumor 1 (WT1) antigen for the treatment of all genetic subtypes of acute myeloid leukemia (AML).
In the fourth quarter of 2021, Intellia initiated screening of patients in the Phase 1/2a study of NTLA-5001 for patients with AML. The Company expects to dose its first patient in the coming weeks and enroll patients throughout the year. Later this year, the Company plans to provide guidance around timing of the first expected data readout, with the goal of demonstrating clinical proof-of-concept for its TCR-based platform.
Modular Platform and Pipeline Expansion

Platform Innovation: Intellia is expanding its industry-leading genome editing platform and scientific leadership through editing, delivery and cell engineering innovations that will enable broader in vivo and ex vivo applications.
Intellia plans to advance at least two new in vivo development candidates by the end of 2022.
The Company expects to nominate its first allogeneic ex vivo development candidate by the first half of 2022.
The Company plans to highlight additional advances to its proprietary technology capabilities, including both genome editing and delivery tools, at upcoming scientific conferences in 2022.
Corporate Updates:

In January, Intellia and Kyverna Therapeutics announced a licensing and collaboration agreement for the development of KYV-201, an allogeneic CD19 CART-cell therapy for the treatment of a variety of B cell-mediated autoimmune diseases. Intellia may exercise an option to lead U.S. commercialization for KYV-201 under a co-development and co-commercialization agreement.
In December 2021, Intellia appointed Derek Hicks as Executive Vice President, Chief Business Officer. Mr. Hicks joins Intellia with more than 25 years of combined business, leadership and biotechnology experience, having most recently served as Head of Business Development at Spark Therapeutics.
Cash Position

Intellia ended the fourth quarter of 2021 with approximately $1.1 billion in cash, cash equivalents and marketable securities.
Intellia’s Presentation at the 40th Annual J.P. Morgan Healthcare Conference

Intellia is scheduled to present virtually at the 40th Annual J.P. Morgan Healthcare Conference on Wednesday, January 12, at 2:15 p.m. ET. A live audio webcast of Intellia’s presentation can be accessed under the Events and Presentations page of the Investors & Media section on the company’s website at www.intelliatx.com. A replay of the webcast will be available on Intellia’s website for at least two weeks following the presentation.

On January 6, 2022 F-star Therapeutics, Inc. (NASDAQ: FSTX), a clinical-stage biopharmaceutical company dedicated to developing next generation bispecific immunotherapies to transform the lives of patients with cancer, reported that Ares Trading S.A., an affiliate of Merck KGaA, Darmstadt, Germany has exercised a fourth licensing option to develop another bispecific program under the ongoing immuno-oncology collaboration (Press release, F-star, JAN 6, 2022, View Source [SID1234598316]). Under the terms of the agreement, Merck KGaA, Darmstadt, Germany will be responsible for all future development and commercialization costs and will pay future success-based milestones and royalties on any net sales, resulting from programs covered by the agreement.

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The two companies have had a long standing and successful partnership and in May of 2019 Merck KGaA, Darmstadt, Germany, exercised its option to bring a first program from the collaboration into its pipeline. In July 2020, Merck KGaA, Darmstadt, Germany took an early option to a second program and in March 2021, a third option was exercised. With the fourth option now exercised, the total potential remaining milestone-based revenue due to F-star from this immuno-oncology collaboration with Merck KGaA, Darmstadt, Germany is approximately $765 million.

Eliot Forster, CEO of F-star Therapeutics, Inc, said: "We were delighted to see the recent data presented by Merck KGaA, Darmstadt, Germany, from our long-standing collaboration at the recent SITC (Free SITC Whitepaper) conference, demonstrating the unique potential of the F-star bispecific platform. This latest licensing option marks another positive milestone in our collaboration and it is exciting to see our partner successfully progress another mAb2 based program. Along with our internal pipeline, we believe all of these next generation immuno-oncology programs will make a real difference to the lives of patients with cancer."

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.