On October 18, 2021 Crinetics Pharmaceuticals, Inc. (Nasdaq: CRNX), a clinical stage pharmaceutical company focused on the discovery, development, and commercialization of novel nonpeptide therapeutics for rare endocrine diseases and endocrine-related tumors, together with 5AM Ventures and Frazier Healthcare Partners, reported the formation of an independently operated new company, Radionetics Oncology. Radionetics aims to develop a deep pipeline of novel, targeted, nonpeptide radiopharmaceuticals for the treatment of a broad range of oncology indications (Press release, Crinetics Pharmaceuticals, OCT 18, 2021, View Source [SID1234591581]).

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Radionetics’ pipeline is based on a broadly enabling platform and intellectual property that will leverage more than a decade of discovery experience within Crinetics. The platform uses nonpeptides as targeting agents designed to deliver therapeutically active radiopharmaceuticals to tumors expressing unique peptide receptors. Radionetics’ initial drug development efforts will center on advancing a collection of 10 potent nonpeptide-targeted radiopharmaceutical candidates and leads, discovered at Crinetics, into clinical imaging and efficacy studies. Radionetics will work independently and with Crinetics to identify additional novel radiopharmaceutical targets and drug candidates for a range of cancer indications.

David Allison, Ph.D., a partner at 5AM Ventures and member of the Radionetics board of directors commented, "Radiopharmaceuticals have emerged as an important class of oncology therapeutics demonstrating survival benefits for patients in multiple tumor settings including prostate cancer and neuroendocrine tumors. We are launching Radionetics with what we believe to be a promising pipeline to expand the utility of radiopharmaceuticals to novel targets. We look forward to building on Crinetics’ world-class expertise in discovery and development of small molecule therapeutics targeting peptide receptors for the benefit of cancer patients."

In conjunction with formation of the company, Radionetics will receive an exclusive world-wide license to the radiotherapeutics technology platform and associated intellectual property from Crinetics for use in developing radiotherapeutics and related radio-imaging agents in exchange for equity, milestones in excess of $1 billion and single-digit royalties on net sales. Radionetics launches with a $30 million private financing with 5AM Ventures and Frazier Healthcare Partners as the sole investors. Radionetics and Crinetics will also engage in a research collaboration to identify drug candidates for multiple additional targets.

"Peptide receptors are a uniquely attractive family of drug targets for precision radiotherapeutics, with more than 120 different family members, many of which are over-expressed in hard-to-treat solid tumors. We are very excited to expand Crinetics’ nonpeptide therapeutics platform into the realm of radiopharmaceuticals with the formation of Radionetics," said Scott Struthers, Ph.D., founder and CEO of Crinetics. "With the launch of Radionetics, Crinetics shareholders will continue to participate in the value of these assets through Crinetics’ equity ownership in the new company as well as through potential milestones and future royalty streams, while at the same time giving the platform the dedicated attention and financing it deserves to fully realize its potential to help the many people around the world in need of new options to treat their cancers." Dr. Struthers has spent his entire scientific and business career seeking to better understand peptide hormone receptors and how to target them with novel therapeutics. As the founder and CEO of Crinetics, he has successfully led and grown the company from a four-person boot-strapped startup to a publicly traded company with multiple clinical stage programs. Dr. Struthers will serve as chairman of the Radionetics board of directors.

Radionetics Leadership
Radionetics launches with a seasoned R&D leadership team, including Crinetics co-founders, Yun-Fei (Frank) Zhu, Ph.D. and Ana K. Kusnetzow, Ph.D., who are assuming roles as chief research officer and vice president of biology, respectively. While at Crinetics Dr. Zhu was vice president of chemistry and a co-inventor of Crinetics’ nonpeptide drug candidates, three of which have now demonstrated clinical proof of concept. Dr. Kusnetzow was most recently the senior director of biology and co-leader of the Crinetics discovery project that gave rise to the nonpeptide targeted radiotherapeutics platform that now forms the basis of the Radionetics pipeline.

In addition, Deborah Slee, Ph.D. will join Radionetics as chief development officer. Dr. Slee was previously senior vice president of nonclinical development and operations at Gossamer Bio and has an extensive track record of advancing multiple drug candidates from discovery into clinical development in oncology and other indications. Brett Ewald, Ph.D. joins as senior vice president & head of strategy and corporate development. Dr. Ewald has extensive experience in early- and late-stage clinical development as well as alliance and portfolio management for oncology products in small and large pharmaceutical companies. Most recently, he was senior vice president of development and corporate strategy at DNAtrix, before which he was a senior member of the clinical operations team at Novartis Oncology.

Additionally, Zachary Hornby, an experienced oncology company leader, entrepreneur and currently CEO of Boundless Bio, will serve as a board member. Prior to joining Boundless Bio, Mr. Hornby was chief financial offer and subsequently chief operating officer at Ignyta, where he took the company public and oversaw development of the company’s portfolio of four clinical stage precision therapeutics for oncology and led the business development process that resulted in Ignyta’s acquisition by Roche for $1.7 billion. Stephen Betz, Ph.D., co-founder and chief scientific officer at Crinetics, will join the Radionetics scientific advisory board.

"Having such an experienced team, Radionetics is well positioned to move expeditiously towards the clinic and full realization of the potential of this platform technology. This is amplified by our collaboration with Crinetics and the direct commitment and participation of key members of the Crinetics founding team who built the underlying technology platform," said Daniel Estes, Ph.D., general partner at Frazier Healthcare Partners, and member of the Radionetics board of directors. "We look forward to building Radionetics into a world-class oncology company focused on radiopharmaceuticals."

On October 18, 2021 Phio Pharmaceuticals Corp. (Nasdaq: PHIO), a biotechnology company developing the next generation of immuno-oncology therapeutics based on its proprietary self-delivering RNAi (INTASYL) therapeutic platform, reported that new data suggesting a systemic immune response can be generated with its lead clinical product candidate, PH-762, after local administration (Press release, Phio Pharmaceuticals, OCT 18, 2021, View Source [SID1234591448]). These data will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 36th Annual Meeting, being held in Washington, D.C. on November 10-14, 2021.

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Presentation Details are as follows:

Title:

Locally administered immunotherapy self-delivering RNAi PH-762 results in abscopal clearance of untreated distal tumors, suggesting systemic immune response, in a murine hepatocarcinoma model

Abstract Number:

869

Author:

Benjamin Cuiffo, et al.

Time and Date:

7:00 am – 8:30 pm ET on 11/12/2021

Location:

Poster Hall – Hall E

Poster presentations will be accessible in person and virtually. Posters will released on the SITC (Free SITC Whitepaper) website at 7:00 am ET on November 12, 2021 and will also be made available on the "Investors – Events and Presentations" section of the Company’s website (click here).

On October 18, 2021 Schrödinger (Nasdaq:SDGR) and Centessa Pharmaceuticals plc ("Centessa") (Nasdaq:CNTA), together with subsidiary Orexia Therapeutics ("Orexia"), reported an exclusive collaboration focused on the discovery of novel therapeutics targeting the orexin-2 receptor (OX2R), which is known to play a role in a broad spectrum of sleep disorders, including narcolepsy (Press release, Centessa Pharmaceuticals, OCT 18, 2021, View Source [SID1234591464]). The collaboration provides Orexia with substantial access to Schrödinger’s entire computational platform as well as Schrödinger’s extensive expertise in ultra-large-scale deployment of its technology.

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Orexia will leverage Schrödinger’s computational platform, including LiveDesign and Free Energy Perturbation (FEP+), which facilitates high-performance calculations for drug discovery to enable accurate prediction of potency at the target of interest. The collaboration will be enabled by Orexia’s structural biology capabilities, including the stabilized OX2R StaR protein exclusively licensed from Sosei Heptares, and high-resolution crystal structures in agonist conformation. The collaboration represents the first time Schrödinger’s technology will be applied in an orexin agonist setting at scale.

"While prevailing treatment approaches only address the symptoms associated with narcolepsy type 1 (NT1), we believe orexin agonists offer a disruptive approach, with the capacity to address the underlying pathology of the disorder. Orexia’s utilization of OX2R stabilized receptors (StaRtechnology) provides the foundation for R&D which could significantly benefit patients with NT1. We look forward to partnering with Schrödinger to complement the discovery and development work we are conducting at Orexia," said Saurabh Saha, M.D., Ph.D., chief executive officer of Centessa.

"Orexia’s asset-centric approach enables us to pick the best technology partners for discovery and development. While we expect to enter IND enabling studies with our lead molecule next year, we are also delighted to work with Schrödinger to enable the acceleration of our discovery efforts for molecules with potentially differentiated clinical profiles. Indeed, the therapeutic possibilities of orexin agonists extend well beyond NT1 into other rare primary hypersomnia disorders, such as narcolepsy type 2 and idiopathic hypersomnia, and into a broad range of additional indications characterized by excessive daytime sleepiness. We are committed to exploring the full potential of orexin agonists to help patients across a wide range of indications," said Mario Alberto Accardi, Ph.D., chief executive officer of Orexia.

"Our research collaboration with Orexia is illustrative of a new approach to help support discovery efforts at biotech companies, where we apply our technology at scale on behalf of our collaborator," stated Ramy Farid, Ph.D., president and chief executive officer of Schrödinger. "The Orexia team brings deep experience in orexin biology and structure-based drug design, and we’re excited to provide Orexia with large-scale access to our leading computational approaches and expertise to accelerate the discovery of novel therapeutics targeting orexin biology."

Under the terms of the agreement, Orexia will be responsible for preclinical research activities, clinical development and commercialization of future product candidates discovered under the collaboration. Schrödinger will receive an upfront software access payment and may become eligible to receive certain preclinical, development, regulatory and commercial milestone payments, as well as low single digit royalties on global net sales.

On October 18, 2021 Prime Therapeutics, a leading pharmacy benefit manager (PBM) serving more than 33 million members, reported that IntegratedRx – Oncology (Press release, Prime Therapeutics, OCT 18, 2021, View Source;oncology-301402335.html [SID1234591491]). This new clinically integrated program streamlines the treatment pathway for members who are fighting cancer so they can now receive their oral oncolytic and companion medications in the clinical setting directly from their oncologist’s clinic or affiliated hospital pharmacy. This promotes lower drug costs, quicker time-to-medication, better adherence and an improved patient and provider experience for Blue Plans and their members.

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The IntegratedRx – Oncology program represents Prime’s channel independent approach of identifying solutions that drive the best financial and quality outcomes for Blue Plans and members. It makes Prime the only large PBM that doesn’t prioritize a central fill specialty pharmacy as the primary model to receive their oral oncolytic medications.

The nationwide rollout of IntegratedRx – Oncology builds on a successful pilot program with McKesson Health Mart Atlas, the largest pharmacy services administrative organization (PSAO) in the U.S., conducted in Florida, Minnesota and the Pacific Northwest earlier this year. The integrated care pilot indicated benefits to providers as well as patients, including:

Shorter fill times allowing patients to begin treatment up to two days faster.
Significantly better medication adherence.
Reduced drug costs.
"We were delighted to work with Prime to innovate and develop this new program that employs a best-in-care integrated dispensing model for cancer medications," said Mark Alwardt, vice president of Medically Integrated Dispensing at McKesson. "At McKesson, we have a patient-first mentality and saw the opportunity to help deliver superior member outcomes through improved therapy management, a collaborative care model and expanded drug access."

"By connecting the care team to the practice pharmacy, IntegratedRx Oncology removes roadblocks that can complicate the cancer care journey," said Joseph Leach, M.D., chief medical officer for Prime and a practicing oncologist. "This type of channel-agnostic approach is a hallmark of Prime’s focus on improving the member and provider experience. An integrated pharmacy-provider model is proven to improve medication adherence and results in better care management. IntegratedRx is designed to bring the pharmacy, caregiver and physician closer together to the patient."

Prime is also collaborating with other national health care companies to operationalize and ensure success of the program, including AmerisourceBergen and Shields Health Solutions. As a leading distributor of specialty pharmaceuticals, AmerisourceBergen is now offering IntegratedRx to physician practice and health systems customers.

"As a company that helped pioneer medically-integrated dispensing programs within independent oncology and launched the first-ever specialty PSAO, we believe in enabling the necessary access to specialty drugs and oral oncolytics in an integrated care setting," said Lisa Harrison, RPh, President of Specialty Distribution at AmerisourceBergen. "The IntegratedRx program enhances the patient and provider experience, and elevates a new model for how oncology care is delivered. We are excited to be a part of this program."

Prime has also partnered with NCODA to launch a new Center of Excellence Accreditation Program Prime will prefer for its new clinically integrated program.

"Allowing medically integrated pharmacies to go beyond the first fill provides the most optimal outcome for the patient and all stakeholders involved," said Michael Reff, NCODA Executive Director. "Developing a model for MIPs several years ago and now collaborating with Prime and seeing them bring it to scale with a formal MIP Accreditation requirement, is a pinnacle point in this mission that brings sustainability, improved clinical experience and better care to millions of patient lives."

"Prime’s IntegratedRx program allows Blue Plans to lead in market with a differentiated care model that benefits their members and clients," added Leach. "We appreciate the willingness of all our program partners to innovate with us on this new offering."

Beginning with Oncology, the IntegratedRx suite of products will streamline medication delivery for various medical conditions. Available to all Blue Plans, several Prime clients will implement IntegratedRx – Oncology starting in the fall of 2021.

On October 18, 2021 B Science SA(Euronext -FR0010557264 -AB) reported that it has been authorized by theFrench Medicine Agency, ANSM, to initiate aPhase I/II study(AB18001)evaluating AB8939 in patients with refractory and relapsed AML and refractory myelodysplastic syndrome(MDS) (Press release, AB Science, OCT 18, 2021, View Source [SID1234591449]).This approval comes just a few weeks after receiving similar authorization from the Canadian Health Authority [1].

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ProfessorNobert Vey, MD, principal investigator of the study and Director of Clinical Research at Institut Paoli-Calmettescommented,"We are very excitedto start the clinical developmentofAB8939. This drugis based on a well-known therapeutic class of compounds which are useful for the treatment of various cancers, however,AB8939 has a superior potential becauseit was designedto overcome common mechanisms of drug resistance.Numerous non-clinical data generated at Institut Paoli-Calmettes are already available suggesting that AB8939 is particularly well-suited for treatment of relapsed/refractory AML".As previously communicated [1], AB8939 is a new generationsyntheticmicrotubule destabilizer with the ability to overcome multidrug resistance and the potential for broad applicability as a potent anticancer drug.

Microtubules play a crucial role in multiple cellular functionswhich makes theman important target for cancer therapy. Indeed, chemotherapies that targetmicrotubules, such as taxanes and vinca alkaloids,are among the most successfulanticancer therapeutics available. Unfortunately, the development of drug resistance(for example, via Pgp efflux pumps that transport the drugs out of the cancer cells)oftenrestrict their clinical efficacy. Key characteristicsof AB8939 arethat it circumventsdifficulties associated with Pgp-dependent multidrug resistanceand is not deactivated by an enzymenamed myeloperoxidase, which is an advantage over existing chemotherapies.Another advantage and distinguishing characteristic of AB8939 is that it is a synthetic drug. The therapeutic potential of AB8939 has beendemonstrated through a series of preclinicalexperiments [2–4].

Invivodata from a highly resistant Ara-C patient derived xenograft (PDX)mouse modelshowed that AB8939,administered alone or in combination with Ara-C, increasedsurvivalrelative tosingle agent Ara-C, with an accompanying significant reduction of blasts in blood and decrease intumor growth [2].Ara-C is considered the clinically most relevant cytotoxic drugfor AML treatment.In another example, cancerous tumors from patients suffering from resistant acute megakaryoblastic leukemia (an AML subtype)were transplanted into mice. Data showed a complete response in mice treated with AB8939, as compared with rapid disease progression in controlanimals [3]. No apparent toxicity was observed during the time course of the treatment.Based on these results, AB8939 was granted orphan drug designation for AML from the U.S. Food and Drug Administration (FDA)[5].

Page 2/3The first indication AB8939 is being developedfor is acute myeloid leukemia (AML),a rapid proliferating hematological cancerthat originates in the bone marrow and quickly moves into the blood.Cytarabine (Ara-C) isthe current standard chemotherapy for AML treatment, however, drug resistance is a major limitation to successful therapy.

AB8939 therefore has strong potential as asecond or third-line treatment in AML patients who are unfit to receive intensive chemotherapy.The advantageous mechanistic characteristics of AB8939 mean that it is potentially applicable to a large number of other oncology indications currently treated by microtubule-inhibitor drugs (such astaxanes and vinca alkaloids)and in particular hematological cancers. The envisioned strategy is to position AB8939 in patients with abnormal cytogenetics that make these patients unresponsive to first-line therapy.AB8939 was entirely discovered by the laboratories of AB Science, which retains full ownership of intellectual rights, and is anexample of AB Science’s focus on innovative drug development focused on improving patients’ lives. About Study AB18001Study AB18001, titled‘A Phase 1/2 Study to Assess the Safety, Pharmacokinetics, and Efficacy of Daily Intravenous of AB8939 in patients with Relapsed/Refractory Acute Myeloid Leukemia’, has a multi-stage design.

Thefirst part is a dose escalation study thataims to determine the safety and tolerability of intravenous AB8939 in patients with refractory or relapsed AML or patients with refractory MDS,and to determine the recommended dose for the second-stage dose expansion study. This dose expansion study aims to determine the schedule for aPhase 2 trial in patients with relapsed/refractory AML and to also provide an early efficacy (response rate) assessment of AB8939.

About acute myeloid leukemia (AML)
Acute myeloid leukemia (AML) is a serious, life-threating condition and the most common cause of leukemia-related mortality, with a majority of patients facing a highly unsatisfactory prognosis. As such, AML represents an unmet medical need, with limited therapeutic options for patients who are refractory or too frail to benefit from potentially curative but highly toxic treatment, or for those patients that have relapsedfollowing a first complete response. The prevalence of AML in western countries is around 1 per 5,000 persons [6], corresponding to around 100,000 cases in Europe and 60,000 in the USA. Among AML patients, it is estimated that approximately 50% of the patients will not have stem cell transplantation and will relapse. Therefore, the estimated targeted population of AB8938 in AML is around 80,000 people in Europe and the US.

References
[1] Press release dated September 22, 2021
[2] Goubard A, Humbert M, Mansfield C, Hermine O, Dubreuil P, et al. In Vivo Assessment of the Next Generation Microtubule-Destabilizing Agent AB8939 in Patient-derived Xenograft Models of Acute Myeloid Leukemia.Blood (2019) 134 (Supplement_1): 5142.doi.org/10.1182/blood-2019-127143[3]Goubard A, Humbert M, Mansfield C, Hermine O, Dubreuil P, et al. AB8939, a Microtubule-DestabilizingAgent with Potential to Overcome Multidrug Resistance, is Active Across the Range (M0–M7) of Acute Myeloid Leukemia Subtypes. Blood (2019) 134 (Supplement_1): 5154.doi.org/10.1182/blood-2019-127021[4]Humbert M, Goubard A, Mansfield C, Hermine O, Dubreuil P, et al. Anticancer Activity of a Highly Potent Small Molecule Tubulin Polymerization Inhibitor, AB8939. Blood (2019) 134 (Supplement_1): 2075. doi.org/10.1182/blood-2019-122540[5] Press release dated November 7, 2019
Page 3/3[6] National Cancer Institute (View Source)