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Anaveon doses first patient in a Phase I/II study to evaluate the safety, dosing and clinical activity of ANV419 in patients with solid tumors

On June 24, 2021 Anaveon, a clinical stage, immuno-oncology company, reported that it has successfully dosed the first patient in a Phase I/II open label study of ANV419, a powerful and selective interleukin-2 (IL-2) agonist as a monotherapy in patients with advanced solid tumors (Press release, Anaveon, JUN 24, 2021, View Source [SID1234584303]). ANV419 has been designed to overcome known challenges with tolerability and selectivity of recombinant human IL-2.

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The study is an open-label, multi-center Phase I/II trial evaluating the safety, tolerability, dose finding and clinical efficacy of ANV419 in patients with advanced solid tumors. Recruitment is ongoing in Spain. Link to the study.

"Dosing our first patient represents an important validation of our approach and is a significant milestone for Anaveon,"said Dr Christoph Bucher, Chief Medical Officer of Anaveon. "We have initiated a multi part, first-in-human dose finding study of ANV419 as a monotherapy in patients with solid tumors. Our compound has excellent tolerability in non-human primates and marked efficacy in a variety of tumor models and elicits strong and selective proliferation of effector cells in multiple settings."

Martin Murphy, Chief Executive of Syncona Investment Management Limited, added:"We are encouraged by Anaveon’s strong progress since our first investment in the company in 2019. The first patient dosing comes off the back of pre-clinical data which has shown that ANV419 has the potential to be a best-in-class asset. Whilst not without risk, the clinical data generated by the company will be a critical driver of value and there is a fast timeline for the company to show differentiation against competing products. We are excited about its potential."

ANV419 is a novel IL-2/anti-IL-2 fusion protein with preferential signaling through the IL-2 beta/gamma receptor. It has antibody-like pharmacology, behavior and stability and selectively stimulates the proliferation of CD8 T cells and NK cells without promoting the expansion of Regulatory T cells (Tregs). In non-human primate studies, ANV419 demonstrated excellent tolerability, a highly favorable safety profile and pharmacokinetics with strong in-vivo expansion of NK and CD8 T cells but not Tregs. No significant changes in body weight or blood pressure were seen at any dose during the entire study period and no signs of capillary leak syndrome were observed. Anaveon expects to report initial clinical safety and pharmacokinetic (PK)/ pharmacodynamic (PD) data by the end of 2021.

Anaveon was founded in December 2017 by Andreas Katopodis, previously Director at the Autoimmunity, Transplantation & Inflammation Group at the Novartis Institutes for BioMedical Research and Onur Boyman, Professor and Chair in the Department of Immunology at the University of Zurich. The Company is developing selective IL-2 Receptor Agonists, which have the potential to therapeutically enhance a patient’s immune system to respond to tumors. In the body, human IL-2 stimulates a type of immune cell, called a T-cell, to multiply and become activated. Activated T-cells are able to attack tumors and, consistent with this approach, human IL-2 is already approved as a therapeutic for the treatment of metastatic melanoma and renal cancer; however, due to lack of specificity, human IL-2 has severe, dose-limiting side effects and a short half-life that requires frequent infusions. The lead compound, ANV419, is designed to preferentially signal through the IL-2 beta/gamma receptor and therefore overcome known challenges of human IL-2. This novel type of therapeutic, if approved, could potentially have a wide utility in oncology, including in combination with cell therapies, vaccines, checkpoint inhibitors and radiotherapy.

Scandion Oncology reports positive interim results from the CORIST Phase II study

On June 24, 2021 Scandion Oncology A/S reported that positive results from the dose-finding part 1 of the CORIST Phase II study (Press release, Scandion Oncology, JUN 24, 2021, View Source,c3373635 [SID1234584302]). A well tolerated dose of SCO-101 in combination with the chemotherapy regimen FOLFIRI has been determined and the SCO-101 treatment in the optimized combination resulted in notable potentiation of the biological activity of FOLFIRI. Furthermore, the CORIST study has identified the oncogene RAS as a predictive biomarker, which will be used to optimize the inclusion of patients in part 2. These positive data, have significantly de-risked the further development of SCO-101 and the company is now ready to advance to the proof-of-concept study (part 2) of CORIST.

Part 1 of the CORIST study demonstrates the potential of SCO-101

"The interim CORIST data support our development plans for SCO-101 and at the same time pioneer the important perspectives around the platform potential of SCO-101, where we revert cancer drug resistance in various cancer diseases. We are looking forward to utilizing these learnings in our overall aim of building value for the patients, society and shareholders. We will communicate more about our plans and strategy at our Capital Market Day in September," says Bo Rode Hansen, President & CEO at Scandion Oncology.

Scandion Oncology, The Cancer Drug Resistance Company, is pleased to announce that the Company has obtained positive interim results from the CORIST trial, which substantiates the path for the further development of SCO-101. The CORIST Phase II study is aimed at combating cancer drug resistance in patients with metastatic colorectal cancer (mCRC) with acquired resistance to the chemotherapy regimen FOLIFRI. The patients enrolled in the trial have all failed prior standard chemotherapy due to resistance and have entered a terminal stage of their disease. Several positive take-home messages can be extracted from the data:

Well tolerated dose of SCO-101 in combination with FOLFIRI established
SCO-101 potentiates the biological effect of FOLFIRI in patients
Treatment benefit appears higher in patients without mutation in the RAS gene (RAS wild-type)
RAS biomarker enables de-risking of part 2 proof-of-concept study with SCO-101 in combination with FOLFIRI, in RAS wild-type patients with mCRC resistant to FOLFIRI
To exploit the new knowledge of the biomarker, the clinical protocol for part 2 of CORIST will be amended. Part 2 will commence as soon as the amendment is approved by the regulatory authorities. Timelines for read-out of CORIST part 2 may extend into Q3, 2022 due to this optimization.

All together, the results from the part 1 of the CORIST study have added significantly to our understanding of the effects of SCO-101 and consequently, de-risked the CORIST program.

We are ready to advance to the proof-of-concept part of the CORIST study

"We are satisfied finding a safe dose of SCO-101 in combination with FOLFIRI which displays biological activity in the patients and also favorably changes the adverse effects of the chemotherapy. We are further excited to have identified RAS as a predictive biomarker in the study. This enables us to tailor the treatment to patients who tolerate the treatment best and thereby have a higher likelihood to benefit from the treatment. We thank the patients and investigators who are participating in the trial," says Peter Michael Vestlev, CMO at Scandion Oncology.

Important data collected and predictive biomarker identified

The objective of CORIST part 1 was to study safety, tolerability and early effect measures of SCO-101 in combination with FOLFIRI in patients with metastatic colorectal cancer (mCRC) with acquired resistance to the chemotherapy regimen FOLIFRI. Part 1 of the CORIST study included 12 patients in the first cohort and 6 patients in the second cohort. The patients continue on treatment with SCO-101 and FOLFIRI until progression. Patients from both cohorts are still on treatment in the study, and the preliminary assessment of data show that:

Dose determination: Well tolerated dose of SCO-101 in combination with FOLFIRI has been determined (MTD), and the recommended dose for part 2 of the study has been identified. Repeated daily doses of SCO-101 in combination with a reduced FOLFIRI dose was well tolerated at exposure levels expected to be clinically relevant in this very fragile patient population.

Good safety profile: No treatment related grade 3 or 4 events were observed at the MTD dosis which is very encouraging. Only mild gastrointestinal adverse reactions were observed related to treatment, which is otherwise a common dose limiting adverse reaction to FOLFIRI. The most commonly observed grade 3 or 4 adverse reaction in the first cohort was neutropenia (reduced levels of white blood cells).
SCO-101 potentiates the effect of FOLFIRI: The combination with SCO-101 resulted in a notable potentiation of the biological effect of FOLFIRI on cells targeted by the chemotherapy (e.g. white blood cells and hair follicles).
Predictive biomarker identified: The RAS mutation status of the cancer at diagnosis was identified as a biomarker for segmentation of patients for the treatment with SCO-101 and FOLFIRI. Patients without mutation in the RAS gene (RAS wild-type) tolerated higher doses of SCO-101 and FOLFIRI. Patients with RAS wild-type also stayed longer on treatment than RAS mutated patients. The identified RAS biomarker is present in 50% of all mCRC patients and is already available from the initial diagnosis of the patients before inclusion in the CORIST study. The biomarker will be used for patient inclusion in part 2 of the study.
Preliminary effect measure: Eight of the included patients in CORIST part 1, were identified as RAS wild-type. Five of these eight patients have shown stable disease for more than eight weeks. Two of the five patients experienced a reduction in tumor volume (<30%). One patient has been on trial for more than 24 weeks and is still on therapy as part of the study. All patients in the RAS mutated group have experienced progressive disease after the first status scan.
Following conclusion of part 1, the study will advance to part 2 which will continue the focus on safety, tolerability and efficacy parameters, to establish proof-of-concept for SCO-101 in combination with FOLFIRI.

Timelines adjusted due to required amendment and reduction in eligible patient population

The de-risking of part 2 of the study by only including patients positive for the recently identified predictive biomarker, requires approval of an amendment from the regulatory authorities before part 2 can be initiated. The amendment will be submitted in July and approval is expected within 1-2 months following submission.

Due to the required amendment and the reduction in the eligible patient population for part 2 (RAS wild-type patients), timelines for reporting of results from part 2 may extend into Q3, 2022. The previous plan was to present results in Q1-Q2, 2022.

Additional trial sites in Denmark and abroad are currently being opened to increase recruitment rate and minimize the anticipated change in reporting timelines.

Design of CORIST part 2

The design for part 2 of the study is a standard single arm phase II study with the aim of further assessing safety, tolerability and preliminary effect of SCO-101 in combination with FOLFIRI. The primary efficacy objective is assessment of response (tumor reduction) and secondary efficacy objectives include assessment of Clinical benefit (Stable Disease, Progression Free Survival (PFS), Overall Survival (OS)) as well as biomarker assessment and correlation to treatment tolerability and outcome. Part 2 of the CORIST phase II study will include 25 patients.

Audiocast today, June 24 at 10:00 am CEST

Scandion Oncology A/S will be hosting an audiocast on June 24 at 10:00 am CEST to present the results from the read-out of the CORIST part 1 study, followed by a Q&A session. Representing the company will be President & CEO, Bo Rode Hansen and CMO, Peter Michael Vestlev. Please login to the audiocast via View Source

This information is information that Scandion Oncology A/S is obliged to make public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact person set out above, on June 24, 2021 at 8:00 am CEST.

HUTCHMED Announces Pricing of Global Offering

On August 23, 2021 HUTCHMED (China) Limited ("HUTCHMED" or the "Company") (Nasdaq/AIM: HCM) reported the pricing of its global offering (the "Global Offering") of 104,000,000 new ordinary shares (the "Offer Shares") which comprises an international offering (the "International Offering") and a Hong Kong public offering (the "Hong Kong Public Offering") in connection with a primary listing of its ordinary shares (the "Shares") on the Main Board of the Stock Exchange of Hong Kong Limited (the "SEHK") (Press release, Hutchison China MediTech, JUN 23, 2021, View Source [SID1234586913]).

The final offer price for both the International Offering and the Hong Kong Public Offering (the "Offer Price") has been set at HK$40.10 per Share, which is equivalent to approximately US$25.82 per American depositary share ("ADS") or £3.70 per Share. Each ADS represents five ordinary shares of the Company. The Company has set the Offer Price by taking into consideration, among other factors, the closing price of the ADSs on the Nasdaq Global Select Market ("Nasdaq") and Shares on the AIM market of the London Stock Exchange on June 22, 2021, the latest trading day before pricing. Subject to approval from the SEHK, the Shares are expected to begin trading on the Main Board of the SEHK on June 30, 2021 under the stock code "13".

The gross proceeds to the Company from the Global Offering, before deducting underwriting fees and the offering expenses, are expected to be approximately HK$4.17 billion. In addition, the Company has granted the international underwriters an over-allotment option, exercisable from the date, expected to be on June 30, 2021, on which the Shares are first listed and from which dealings in the Shares are permitted to take place on the Main Board of the SEHK (the "Listing Date") until 30 days after the last day for lodging applications under the Hong Kong Public Offering, to require the Company to issue up to an additional 15,600,000 new Shares at the Offer Price.

The Company will receive all of the net proceeds from the Global Offering and plans to use the net proceeds from the Global Offering primarily to advance its late-stage clinical programs as well as its pipeline of clinical-stage and preclinical drug candidates, further strengthen its commercialization, clinical, regulatory and manufacturing capabilities, fund potential global business development and strategic acquisition opportunities and for general corporate purposes.

Morgan Stanley Asia Limited, Jefferies Hong Kong Limited and China International Capital Corporation Hong Kong Securities Limited are the joint sponsors for the Global Offering.

Information about the Global Offering
Sales of Shares outside of Hong Kong (other than certain Shares which were sold to investors in reliance on Regulation S or another exemption from the registration requirements of the U.S. Securities Act of 1933) initially offered in the United States and sold outside the United States that may be resold from time to time in the United States are being offered pursuant to an automatically effective shelf registration statement that was previously filed with the U.S. Securities and Exchange Commission (the "SEC"). A preliminary prospectus supplement relating to and describing the terms of the Global Offering was filed with the SEC and is available on the SEC’s website at www.sec.gov. The final prospectus supplement relating to the Global Offering will be filed with the SEC and will be available on the SEC’s website at www.sec.gov. When available, an electronic version of the prospectus supplement and the accompanying prospectus relating to these securities, as filed with the SEC, may be obtained for free by mailing the request to: Morgan Stanley & Co. LLC, 180 Varick Street, 2nd Floor, New York, NY 10014, Attention: Prospectus Department, or E-mail: [email protected]; Jefferies Hong Kong Limited, Email: [email protected]; and China International Capital Corporation Hong Kong Securities Limited, Email: [email protected].

This announcement is not directed to, or intended for distribution or use by, any person or entity that is a citizen or resident or located in any locality, state, country or other jurisdiction where such distribution, publication, availability or use would be contrary to law or regulation or which would require any registration or licensing within such jurisdiction.

The 104,000,000 new Shares to be issued by HUTCHMED pursuant to the Global Offering ("New Shares") will, when issued, be credited as fully paid and will rank pari passu in all respects with the existing ordinary shares of HUTCHMED, including the right to receive all dividends and other distributions declared, made or paid in respect of such Shares after the date of issue of the New Shares.

Application will be made to the London Stock Exchange for the 104,000,000 New Shares to be admitted to the AIM market operated by the London Stock Exchange ("Admission"). It is expected that Admission will become effective at 8:00 a.m. UK time on June 30, 2021.

Following Admission and prior to any exercise of the over-allotment option, the issued share capital of HUTCHMED will consist of 848,515,660 Shares of US$0.10 each, with each Share carrying one right to vote and with no Shares held in treasury. This figure may be used by shareholders as the denominator for the calculations by which they could determine if they are required to notify their interest in, or a change to their interest in, HUTCHMED under the Financial Conduct Authority’s Disclosure Guidance and Transparency Rules. For illustrative purposes only, 848,515,660 Shares would be equivalent to 848,515,660 depositary interests (each equating to one ordinary share) which are traded on AIM or, if the depositary interests were converted in their entirety, equivalent to 169,703,132 ADSs (each equating to five Shares) which are traded on Nasdaq. A further announcement will be made if the over-allotment option is exercised.

This announcement contains inside information for the purposes of Article 7 of Regulation (EU) No 596/2014 (as it forms part of retained EU law as defined in the European Union (Withdrawal) Act 2018).

Chasing ‘Holy Grail’ STAT3 Target, Houston Startup Refuels with $74M to Zero in on Liver Cancer

On June 23, 2021 Tvardi reported that it launched out of Houston with the promise of finally developing the right inhibitors for the Holy Grail target of STAT3 — under the guidance of serial entrepreneur Ron DePinho and his colleague David Tweardy, a leading expert in the field. Almost three years later, they say they have the proof of concept data to keep going (Press release, Tvardi Therapeutics, JUN 23, 2021, View Source [SID1234585975]).

It’s good enough for a $74 million Series B, a big jump from the $9 million they got in the last round and, CEO Imran Alibhai would add, a reflection of the rep his team has built.

In Phase I dose escalation studies involving patients with solid tumors who have failed all other treatments, the lead compound was shown to have downregulated the STAT3 activity of interest: blocking it from becoming phosphorylated by the receptors it typically interacts with.

"The topline news is that in over half of our patients, we’ve seen clinical benefit" in the form of tumor stabilization, shrinkage or even partial responses, he said. "That drove a lot of interest, but beyond that what’s been striking has been the safety."

He believes the secret lies in focusing on preventing the activation of STAT3, which drives the nuclear function related to disease, but not trying to remove it from the system, degrade it, or break it too much. The small window, after all, is what makes targeting STAT3 so tricky despite it being a top 5 target for cancer.

By the first half of next year, Tvardi expects to wrap up the Phase I trial and zero in on hepatocellular carcinoma in Phase II trials — while also starting to study the drug for fibrosis.

"When you think about growth and differentiation in tumors, and metastases, there’s probably three or four legs to the stool, and STAT3 is definitely one of those. Right? It is a central node," Alibhai said. "When it comes to fibrosis, there is one leg to the stool. And STAT3 modulates that pathway. And so if you could find a safe drug that actually targets STAT3, you can potentially see some really beautiful data."

Others have arrived at the same conclusion, with a small band of startups heralding new approaches such as protein degradation to target STAT3, Sanofi-partnered Kymera and Medicxi’s Janpix (now part of Centessa) among them.

For his part, Alibhai said he welcomes more options for patients and hopes Tvardi’s oral dosing small molecule treatment can set itself apart. Besides, it is not trivial to make drugs that can even get into the clinic.

"What the true test is: Can you actually get in, be safe, and be very very very targeted in the case of STAT3?" he noted. "Because there are multiple roles for STAT3 in every cell, and so we need to make sure that we’re targeting appropriately for the role that we’re interested in."

The small company is already working on a second-generation molecule that will be three to eight times more potent than the lead candidate, he said. And their new investors are in for the long game, giving them the option to either jump straight into an IPO next or raise another crossover round and, more importantly, "do something interesting."

Slate Path Capital, Palkon Capital, ArrowMark Partners and 683 Capital joined the round, with significant support from Sporos Bioventures and other existing investors.

Rubius Therapeutics Announces First Patient Dosed with RTX-240 in Combination with KEYTRUDA® (pembrolizumab) in Ongoing Phase 1/2 Clinical Trial for the Treatment of Advanced Solid Tumors

On June 23, 2021 Rubius Therapeutics, Inc. (Nasdaq:RUBY), a clinical-stage biopharmaceutical company that is genetically engineering red blood cells to create an entirely new class of cellular medicines called Red Cell Therapeutics, reported that the first patient has been dosed in a new Phase 1 arm of the ongoing Phase 1/2 clinical trial of RTX-240 in combination with KEYTRUDA (pembrolizumab)1 for the treatment of patients with relapsed/refractory or locally advanced solid tumors (Press release, Rubius Therapeutics, JUN 23, 2021, View Source [SID1234584708]). To be eligible for the trial, patients must have disease that is relapsed or refractory to an anti-PD-1 or PD-L1 therapy.

"RTX-240 is designed to activate and expand a patient’s own immune cells to mount a broad and potent anti-tumor response. Combining an immune agonist with a PD-1 checkpoint inhibitor has the potential to prevent the cancer from evading the immune response. The RTX-240 and pembrolizumab combination is anticipated to drive activated T cells and NK cells into the tumor microenvironment with the potential to overcome resistance to PD-1 inhibition," said Christina Coughlin, M.D., Ph.D., chief medical officer at Rubius Therapeutics. "Given the favorable emerging safety profile and promising initial clinical activity reported as part of our initial clinical results from the ongoing Phase 1 monotherapy trial of RTX-240 in advanced solid tumors, we believe that the combination with pembrolizumab has the potential to provide significant benefit to patients with disease that is relapsed or refractory to prior anti-PD-1 or PD-L1 therapy."

"Despite recent advances in cancer immunotherapy, there remains a need for new combination approaches that broaden the benefits of immunotherapy in patients with solid tumors following treatment with checkpoint inhibition," said Omid Hamid, M.D., Chief of Translational Research and Immunotherapy, Director of the Phase 1 Immuno-Oncology Program of The Angeles Clinic and Research Institute, a Cedars-Sinai Affiliate, and RTX-240 investigator. "The exciting initial safety and efficacy data from the ongoing monotherapy Phase 1 clinical trial make RTX-240 a potentially promising candidate for the treatment of cancer, and we are excited to work with Rubius to evaluate RTX-240 in combination with pembrolizumab."

RTX-240 is engineered to express a co-stimulatory molecule, 4-1BB ligand, and a cytokine, IL-15TP, on the cell’s surface, and is designed to broadly stimulate the immune system by activating and expanding both natural killer (NK) cells and T cells to generate a potent anti-tumor response. Pembrolizumab is a humanized monoclonal immunoglobulin G4 antibody (IgG4 mAb) with high specificity of binding to the programmed cell death protein-1 (PD-1) receptor, thus inhibiting its interaction with programmed cell death ligand 1 (PD-L1) and programmed cell death ligand 2 (PD-L2). Based on in vitro data, pembrolizumab has high affinity and potent receptor blocking activity for PD-1. Pembrolizumab is indicated for the treatment of patients across several indications as monotherapy and in combination with numerous therapies.

About the RTX-240 Phase 1/2 Clinical Trial
This is a Phase 1/2 open label, multicenter, multidose, first-in-human dose-escalation and expansion study designed to determine the safety and tolerability, pharmacokinetics, maximum tolerated dose and a recommended Phase 2 dose and dosing regimen of RTX-240. The trial will also assess the pharmacodynamics of RTX-240 measured by changes in T and NK cell number and function relative to baseline and anti-tumor activity. The trial has three separate Phase 1 arms: an ongoing monotherapy dose escalation arm in adults with relapsed/refractory or locally advanced solid tumors, an ongoing monotherapy dose escalation arm in adults with relapsed/refractory acute myeloid leukemia, and a combination therapy dose escalation arm with pembrolizumab in adults with relapsed/refractory or locally advanced solid tumors. The monotherapy arm of the trial in advanced solid tumors includes a Phase 2 expansion in specified tumor types.