On January 24, 2022 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation for eltanexor, a novel oral, Selective Inhibitor of Nuclear Export (SINE) compound, for the treatment of myelodysplastic syndromes (MDS) (Press release, Karyopharm, JAN 24, 2022, View Source [SID1234606723]). MDS are a group of diseases characterized by ineffective production of the components of the blood due to poor bone marrow function with a risk of progression to acute myeloid leukemia.

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Karyopharm is currently investigating eltanexor in an ongoing open-label Phase 1/2 study as a single-agent or in combination with approved and investigational agents in patients with several types of hematologic and solid tumor cancers (KCP-8602-801; NCT02649790). Previously, Karyopharm reported positive data from an investigator-sponsored Phase 1 study evaluating single-agent eltanexor in patients with hypomethylating agent (HMA)-refractory MDS, where eltanexor demonstrated a 53% overall response rate and median overall survival of 9.9 months. This compares favorably to historical survival of four to six months for HMA-refractory MDS patients.

Approximately 15,000 people are diagnosed with intermediate-to-high risk MDS each year in the U.S.1 HMAs are the current standard of care for newly diagnosed, higher-risk MDS patients. However, only 40-60% of patients respond, with these responses typically lasting less than two years.2 The prognosis in HMA-refractory disease is poor, with a median overall survival of four to six months.3,4 There are currently no approved therapies for HMA- refractory MDS.

"We are pleased to receive the FDA’s orphan drug designation for eltanexor in MDS and believe it reinforces eltanexor’s potential to improve clinical outcomes for patients with HMA-refractory MDS," said Richard Paulson, President and Chief Executive Officer of Karyopharm. "We are focused on advancing our ongoing clinical trials and remain steadfast in our commitment to bringing this new treatment option to patients and their families."

Orphan drug designation by the FDA is granted to promote the development of drugs that target conditions affecting 200,000 or fewer U.S. patients annually and are expected to provide a significant therapeutic advantage over existing treatments. Orphan designation qualifies a company for certain incentives that apply across all stages of drug development, including the potential for seven years of market exclusivity following marketing approval, tax credits on qualified U.S. clinical trials, eligibility for orphan drug grants, and exemption from certain administrative fees.

About Eltanexor

Eltanexor (KPT-8602) is an investigational novel SINE compound that, like selinexor, functions by binding with, and inhibiting, the nuclear export protein, XPO1, leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to lead to the selective induction of apoptosis in cancer cells, while largely sparing normal cells.

In preclinical models, eltanexor has a broad therapeutic window with minimal penetration of the blood brain barrier and, therefore, has the potential to serve as another SINE compound for cancer indications. Following oral administration, animals treated with eltanexor show lower percentage of body weight loss and improved food consumption than animals similarly treated with selinexor. This allows more frequent dosing of eltanexor, enabling a longer period of exposure than is possible with selinexor.

Eltanexor is an investigational medicine and has not been approved by the United States Food and Drug Administration or any other regulatory agency.

On January 24, 2022 ITM Isotope Technologies Munich SE (ITM), a leading radiopharmaceutical biotech company, reported that its partners Bruce Power and Isogen (a partnership between Kinectrics and Framatome) have completed the installation of a groundbreaking Isotope Production System (IPS), becoming the first power reactor in the world with the installed capability to produce Lutetium-177 (Lu-177), a medical isotope used in the treatment of various cancers, such as neuroendocrine tumors and prostate cancer (Press release, ITM Isotopen Technologien Munchen, JAN 24, 2022, View Source [SID1234606741]). This system will also have the ability to produce other isotopes for medical uses over the long term.

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"This installation of the IPS is an exciting milestone on our journey to becoming the first power reactor in the world to provide a scalable, game-changing solution in the supply of life-saving medical isotopes for the global medical community," said James Scongack, Bruce Power’s Chief Development Officer and Executive Vice President, Operational Services. "Our medical Isotope Program and the IPS installation are a result of years of innovation and development in partnership with Isogen (a Framatome and Kinectrics company), Saugeen Ojibway Nation, and ITM; and will provide large-scale capacity to help produce medical isotopes, which will be used across the world in new treatments to fight cancer."

With the new system installed, activities will now shift to planned commissioning along with preparation activities for commercial production that will follow once these activities and regulatory submissions are successfully completed.

"Ontario is leading the way in the production and supply of medical isotopes around the world," said Hon. Todd Smith, Ontario’s Minister of Energy. "I’m proud of the innovative work being done by Bruce Power and its partners in the supply chain, including Framatome and Kinectrics. Their efforts are helping to further cement our position as an international isotope superpower, while providing critical medical tools to help meet the needs of patients battling cancer."

Lu-177 offers doctors an alternative to traditional chemotherapy by deploying a "seek-and-destroy" dose to target cancer cells while limiting damage to surrounding healthy tissues and organs.

The IPS was developed and manufactured by Isogen, a joint venture between Framatome and Kinectrics, that is focused on developing innovative isotope production technologies.

"The installation and successful transfer of the first target marks a major accomplishment and successful implementation of Framatome Healthcare technology; the first Isotope Production System (IPS) in a power reactor for commercial production of therapeutic medical isotopes," said Curtis Van Cleve, President and CEO of Framatome Canada Ltd. "We applaud the dedication and efforts of our partners, at Bruce Power, Saugeen Ojibway Nation, Kinectrics, ITM and our team, and the support of their families that allowed them to see this installation through."

"The installation of the IPS is the result of countless hours of support from many people at Bruce Power, Framatome, Kinectrics, Saugeen Ojibway Nation and our suppliers. The entire team demonstrated tremendous dedication, especially during the pandemic." said David Harris, CEO of Kinectrics. "This was a critical step to enable the production of Lutetium-177 for our partner, ITM, and to fortifying a strong, reliable, and large-scale global supply chain of life-saving isotopes, that both physicians and patients can depend on."

With its new IPS system, Bruce Power will conduct the irradiation of Ytterbium-176 (176Yb) as a first step in the production of no-carrier-added Lutetium-177 (n.c.a. 177Lu). Processing of the irradiated Ytterbium-176 for the production of n.c.a. Lutetium-177 as well as the global supply of n.c.a. 177Lu will be handled by ITM.

"The successful installation of this production site builds an important milestone in our partnership with Bruce Power and Isogen to scale-up the production of high-quality medical radioisotopes," said Steffen Schuster, CEO at ITM. "We look forward to the upcoming launch of the IPS system and are proud to contribute with our unique manufacturing methodology to yield high-quality n.c.a. 177Lu and to make it accessible for cancer patients worldwide."

The installation of the IPS is a significant step in the landmark isotope project, which is a partnership that began more than three years ago with over 400 dedicated professionals working on various stages of the project.

In November 2021, Bill Walker, MPP of Bruce-Grey-Owen Sound, introduced a Private Member’s motion – which passed with all party support – to assert Ontario’s leadership role in the production and supply of medical isotopes as a strategic priority for the province. Today’s announcement exemplifies that Ontario continues to be at the forefront of medical isotope technology.

"I want to congratulate Bruce Power, Framatome and Kinectrics on this important accomplishment," said MPP Walker. "Ontario has long been looked to as a leader in the medical isotope space, and these partners are playing an important role in the global supply chain to provide patients around the world with life-saving cancer treatments and diagnostic tools."

Bruce Power will market the new isotope supply in an historic collaboration partnership with Saugeen Ojibway Nation (SON). The partnership project with SON, named "Gamzook’aamin Aakoziwin," includes an equity stake for SON and a revenue-sharing program that directly benefits the SON.

"From the initial concept in 2019 to production expected in 2022, our Gamzook’aamin Aakoziwin project is on track to meet an ambitious timeline to have isotope supply ready to meet the increasing demand from doctors and cancer patients around the world," said Chief Lester Anoquot, Chippewas of Saugeen First Nation. "Saugeen Ojibway Nation is proud of the part we have played and will continue to play in this project."

"Short-lived medical isotopes are essential tools for doctors and researchers in the fight against cancer, and this project will provide a much-needed source of these isotopes for patients close to home, in our communities, and around the world," added Chief Veronica Smith, Chippewas of Nawash Unceded First Nation.

"Thanks to the investments being made into the Bruce Power site today we can look to the future and realize a vital role in providing life-saving medical isotopes to the world, while also supplying clean, reliable and low-cost electricity to Ontario, growing the economy and fostering innovation for decades to come," said Hon. Lisa Thompson, Minister of Agriculture, Food and Rural Affairs, and MPP for Huron-Bruce.

On January 24, 2022 OBI Pharma, a Taiwan biopharma company (TPEx: 4174), reported that the first patients have been enrolled in both of the Phase 2 studies of OBI-999, an antibody drug conjugate (ADC) cancer therapy targeting Globo H, and OBI-3424, a prodrug targeting the enzyme aldo-keto reductase 1C3 (AKR1C3) (Press release, OBI Pharma, JAN 24, 2022, View Source [SID1234606757]).

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The Phase 2 cohort expansion part of the OBI-999-001 (ClinicalTrials.gov Identifier: NCT04084366) entitled "A Phase 1/2, Open-Label, Dose-Escalation and Cohort-Expansion Study Evaluating the Safety, Pharmacokinetics, and Therapeutic Activity of OBI-999 in Patients with Advanced Solid Tumors" has now begun enrollment. The Phase 2 part of the study will enroll Globo H expressing patients with pancreatic, colorectal and other high Globo H expression solid tumors in more than ten medical centers in the United States and Taiwan.

The Phase 2 cohort expansion part of the OBI-3424-001 (ClinicalTrials.gov Identifier: NCT03592264) entitled "A Phase 1/2 Study of OBI-3424 in Subjects with Advanced Solid Tumors" has also begun enrollment. This study will enroll AKR1C3 expressing patients with pancreatic and other high AKR1C3 expressing solid tumors in select oncology medical centers in the United States.

OBI’s Chairman and Chief Executive Officer, Michael Chang, PhD, noted "OBI Pharma strives to develop novel therapeutics for cancer patients worldwide. Based upon the impressive Phase 1 safety study and preclinical data of OBI-999 and OBI-3424, we are excited to commence our Phase 2 efficacy and safety study in patients with high Globo H or AKR1C3 antigen expression in solid tumors. We would like to thank the commitment of our international investigators to bring these 1st-in-class cancer therapeutic products to potential patients in our ongoing study."

OBI anticipates completing the enrollment of both Phase 2 studies in the second half of 2023.

About OBI-999

OBI-999 is a novel first-in-class Antibody Drug Conjugate (ADC) with a proprietary linker technology that provides a consistent Drug-to-Antibody ratio (DAR) for cancer treatment that is based on Globo H, an antigen expressed in up to 15 epithelial cancers. OBI-999 uses a Globo H antibody to target cancer cells of high Globo H expression. By releasing a small molecule chemotherapeutic drug through the specificity of the antibody, it directly deploys cytotoxic therapy at the targeted cancer cells. In pre-clinical xenograft animal models in multiple tumor types (gastric, pancreatic, lung and breast), OBI-999 has demonstrated profound tumor shrinkage at various doses. In human Phase 1 study, OBI-999 was well-tolerated, and achieved a favorable safety margin which warrants further clinical development. OBI-999 is currently in a Phase 2 clinical trial (ClinicalTrials.gov Identifier: NCT04084366) in medical centers in the US and Taiwan. OBI Pharma owns global rights to OBI-999.

About OBI-3424

OBI-3424 is a first-in-class novel small-molecule prodrug that selectively targets cancers overexpressing the enzyme aldo-keto reductase 1C3 (AKR1C3), and selectively releases a potent DNA alkylating agent in the presence of the AKR1C3 enzyme. This selective mode of activation distinguishes OBI-3424 from traditional alkylating agents, such as cyclophosphamide and ifosfamide, which are non-selective.

AKR1C3 overexpression has been documented in a number of treatment-resistant and difficult-to-treat cancers including hepatocellular carcinomas (HCC), castrate-resistant prostate cancer (CRPC), and T-cell acute lymphoblastic leukemia (T-ALL). AKR1C3 is highly expressed in up to 15 solid and liquid tumors.

Furthermore, individualized patient selection by staining for AKR1C3 overexpression by immunohistochemistry can be performed based on tumor biopsies or circulating tumor cells to identify patients with other tumor types most likely to respond to treatment with OBI-3424, and thus offering the possibility for a streamlined clinical development strategy.

OBI-3424 is currently in a Phase 2 trial (ClinicalTrials.gov Identifier: NCT03592264) in medical centers in the US. OBI owns global rights to OBI-3424 except the Asia Pacific region.

On January 24, 2022 Kineta, Inc., a clinical stage biotechnology company focused on the development of novel immunotherapies in oncology, reported an upcoming presentation at the 6th Tumor Models for Immuno-Oncology Summit 2022 (Press release, Kineta, JAN 24, 2022, View Source;utm_medium=rss&utm_campaign=kineta-to-present-on-the-companys-piioneer-platform-at-the-6th-annual-tumor-models-for-immuno-oncology-summit [SID1234607393]). Thierry Guillaudeux, PhD, Senior Vice President Immuno-oncology at Kineta, will be presenting an overview of the company’s proprietary PiiONEER Platform and the use of human knock-in models for selecting next generation immunotherapies.

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Kineta’s immuno-oncology PiiONEER Platform was designed for the discovery and development of first or best-in-class immunotherapies that address the major challenges with cancer resistance to current therapies. Utilization of the innate immunity focused PiiONEER Platform has resulted in the development of novel, well characterized fully human antibody therapeutics that are being advanced into formal IND enabling and clinical studies.

"We have developed a world-class innate immunity-focused platform for developing important new immunotherapies to treat patients with cancer" said Thierry Guillaudeux, PhD, Senior Vice President Immuno-oncology at Kineta. "A core component of our PiiONEER Platform is our in vivo knock in models which are the foundation for the development of our novel VISTA and CD27 antibody programs."

Presentation Details:
Title: Use of Human Knock-in Models for Selecting New Generation of Immune Checkpoint Inhibitors
Date: January 26, 7:30AM Pacific Time
Presenter: Thierry Guillaudeux, PhD

On January 24, 2022 BioLineRx Ltd. (NASDAQ/TASE: BLRX), a late clinical-stage biopharmaceutical Company focused on oncology, reported that the Company has completed enrollment of the Phase 1/2a study of its innovative intratumoral cancer vaccine candidate, AGI-134, designed to evaluate the safety and biological activity of AGI-134 in patients with unresectable metastatic solid tumors (Press release, BioLineRx, JAN 24, 2022, View Source [SID1234606705]). Results of AGI-134’s safety and proof of mechanism are anticipated in the first half of 2022.

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"The completion of enrollment of the AGI-134 first-in-man study is a very significant milestone for our Company, especially taking into account the difficulties caused by the COVID-19 pandemic on patient recruitment," stated Philip Serlin, Chief Executive Officer of BioLineRx. "AGI-134, our second clinical-stage oncology asset, has a unique mode of action, applicable to all injectable tumor types. In preclinical models, AGI-134 led to regression of primary tumors, prevented growth of secondary tumors via an abscopal effect, and triggered a vaccine effect that we believe may prevent the development of metastases. This clinical study aims to confirm the proposed mechanism of action and safety profile of AGI-134 in humans, based on which we also plan to explore potential combinations as part of its future clinical development program."

The Phase 1/2a study is a multicenter, open-label study, which recruited a total of 38 patients in the UK, Spain and Israel, and is comprised of two parts. Part 1 was completed, and was an accelerated dose-escalation study in five patients, to determine the maximum tolerated dose and the recommended dose for part 2 of the study. Part 2 is a dose expansion study at the recommended dose in 33 patients, designed to evaluate the safety and tolerability of AGI-134, and to validate AGI-134’s mechanism of action using a wide array of biomarkers. For more information on this Phase 1/2a study, see NCT03593226.

On December 15, BioLineRx announced the formation of an Immuno-Oncology Scientific Advisory Board (SAB) to provide insight and guidance on the Company’s immuno-oncology activities. The SAB, which has provided valuable guidance to the AGI-134 development program, is comprised of recognized key opinion leaders in the fields of cancer immunology, intra-tumoral cancer treatments and clinical development.

About AGI-134
AGI-134 is a synthetic alpha-Gal glycolipid in development for solid tumors that is highly differentiated from other cancer immunotherapies. AGI-134 is designed to label cancer cells with alpha-Gal via intra-tumoral administration, thereby targeting the body’s pre-existing, highly abundant anti-alpha-Gal (anti-Gal) antibodies and redirecting them to treated tumors. Binding of anti-Gal antibodies to the treated tumors results in activation of the complement cascade, which destroys the tumor cells and creates a pro-inflammatory tumor microenvironment that also induces a systemic, specific anti-tumor (vaccine) response to the patient’s own tumor neo-antigens.

AGI-134 has been evaluated in numerous pre-clinical studies. In a mouse melanoma model, treatment with AGI-134 led to regression of established primary tumors and suppression of secondary tumor (metastases) development. Synergy has also been demonstrated in additional pre-clinical studies when combined with an anti-PD-1 immune checkpoint inhibitor, offering the potential to broaden the utility of such immunotherapies, and improve the rate and duration of responses in multiple cancer types. AGI-134 was obtained by BioLineRx through the acquisition of Agalimmune Ltd.