On November 17, 2022 BeiGene (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global biotechnology company, reported that the European Commission (EC) has approved BRUKINSA (zanubrutinib) for the treatment of adult patients with treatment-naïve (TN) or relapsed/refractory (R/R) CLL (Press release, BeiGene, NOV 17, 2022, View Source [SID1234624194]).

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"This approval represents an important milestone for CLL patients and their physicians who now have a new chemotherapy-free treatment option, and an alternative to current BTKi treatment options," said Mehrdad Mobasher, M.D., M.P.H., Chief Medical Officer, Hematology at BeiGene. "Given that BRUKINSA has demonstrated consistent benefit across patient subgroups, regardless of risk status, we believe BRUKINSA could now be the preferred treatment option for newly diagnosed and relapsed/refractory CLL patients."

The EC approval is based on positive results from two Phase 3 clinical trials: SEQUOIA (NCT03336333), in patients with previously untreated CLL, and ALPINE (NCT03734016), in patients with R/R CLL. In these two trials, BRUKINSA demonstrated superior efficacy versus either bendamustine plus rituximab (B+R) or ibrutinib in first-line or R/R CLL, respectively. BRUKINSA is the only BTKi to achieve superiority versus ibrutinib in R/R CLL, as assessed by independent review committee, with an overall response rate (ORR) of 80.4% vs 72.9% (p=0.0264).i Additionally, more BRUKINSA patients than ibrutinib patients had a sustained response at 1 year with rates of 90% vs 78%.i The adverse events within the two trials were consistent with the overall safety profile of BRUKINSA. Subsequent to the regulatory submission, BeiGene announced topline results of the final PFS analysis of the head-to-head ALPINE trial, in which BRUKINSA demonstrated superior PFS compared with ibrutinib in patients with R/R CLL.

Prof. Clemens Wendtner, Head of Hematology and Oncology at Munich Clinic, an academic teaching hospital of the University of Munich, Germany, commented, "BRUKINSA has demonstrated clinically meaningful improvements as a next-generation BTKi over the first generation BTKi, and is proven to be significantly more effective and tolerable. Ensuring medicines are safe and tolerable for this patient population is critical, given the long-term treatment needed for CLL. Combined with the flexible dosing options, this approval offers a practice-changing option for patients with CLL, one of the most common types of leukemia in adults."

"We’re pleased with the significant progress we’ve made to date bringing BRUKINSA to patients with hematological malignancies globally," noted Gerwin Winter, Senior Vice President, Head of Europe at BeiGene. "With this notable approval, we welcome the opportunity to expand BeiGene’s presence in Europe and provide this innovative treatment option to CLL patients across the region."

BRUKINSA is currently approved in the EU for the treatment of adult patients with WM who have received at least one prior therapy or as the first-line treatment for patients unsuitable for chemoimmunotherapy and adult patients with MZL who have received at least one prior anti-CD20-based therapy.

In Europe, BeiGene has now obtained reimbursement for BRUKINSA for the treatment of WM in Austria, Belgium, Denmark, England and Wales, Germany, Iceland, Ireland, Italy, Luxembourg, Scotland, Spain, Switzerland, and The Netherlands, while additional EU countries are currently going through the reimbursement process.

About Chronic Lymphocytic Leukemia (CLL)

A slow-growing, life-threatening and incurable cancer of adults, CLL is a type of mature B-cell malignancy in which abnormal leukemic B lymphocytes (a type of white blood cells) arise from the bone marrow and flood peripheral blood, bone marrow, and lymphoid tissues.ii-iv CLL is one of the most common types of leukemia, accounting for about one-quarter of new cases of leukemia.v In Europe, the estimated incidence is 4.92/100,000 persons per year.vi,vii

About BRUKINSA

BRUKINSA is a small-molecule inhibitor of Bruton’s tyrosine kinase (BTK) discovered by BeiGene scientists that is currently being evaluated globally in a broad clinical program as a monotherapy and in combination with other therapies to treat various B-cell malignancies. BRUKINSA was specifically designed to deliver targeted and sustained inhibition of the BTK protein by optimizing bioavailability, half-life, and selectivity. With differentiated pharmacokinetics compared to other approved BTK inhibitors, BRUKINSA has been demonstrated to inhibit the proliferation of malignant B cells within a number of disease-relevant tissues.

BRUKINSA is supported by a broad clinical program which includes more than 4,700 subjects in 35 trials in more than 25 countries and regions. To date, BRUKINSA is approved in 58 markets, including the United States, China, the European Union Great Britain, Canada, Australia, South Korea, Switzerland, and additional international markets.

BeiGene Oncology

BeiGene is committed to advancing best- and first-in-class clinical candidates internally or with like-minded partners to develop impactful and affordable medicines for patients across the globe. We have a growing R&D and medical affairs team of approximately 3,500 colleagues dedicated to advancing more than 100 clinical trials that have involved more than 20,000 subjects. Our expansive portfolio is directed predominantly by our internal colleagues supporting clinical trials in more than 45 countries and regions. Hematology-oncology, and solid tumor targeted therapies, and immuno-oncology are key focus areas for the Company, with both monotherapies and combination therapies prioritized in our research and development. BeiGene currently has three approved medicines discovered and developed in our own labs: BTK inhibitor BRUKINSA in the U.S., China, the European Union, Great Britain, Canada, Australia, South Korea, Switzerland, and additional international markets; and the non-FC-gamma receptor binding anti-PD-1 antibody tislelizumab as well as the poly adenosine diphosphate-ribose polymerase (PARP) inhibitor pamiparib in China.

BeiGene also partners with innovative companies who share our goal of developing therapies to address global health needs. We commercialize a range of oncology medicines in China licensed from Amgen, Bristol Myers Squibb, EUSA Pharma, and Bio-Thera. We also plan to address greater areas of unmet need globally through our other collaborations including Mirati Therapeutics, Seagen, and Zymeworks.

In January 2021 BeiGene and Novartis announced a collaboration granting Novartis rights to co-develop, manufacture, and commercialize BeiGene’s anti-PD-1 antibody tislelizumab in North America, Europe, and Japan. Building upon this productive collaboration, BeiGene and Novartis announced an option, collaboration, and license agreement in December 2021 for BeiGene’s TIGIT inhibitor ociperlimab that is in Phase 3 development. Novartis and BeiGene also entered into a strategic commercial agreement through which BeiGene will promote five approved Novartis oncology products across designated regions of China.

On November 17, 2022 Ayala Pharmaceuticals, Inc. (Nasdaq: AYLA), a clinical-stage oncology company focused on developing and commercializing small molecule therapeutics for patients suffering from rare tumors and aggressive cancers, reported a poster presentation highlighting interim results from the Phase 2 segment / Part A of the RINGSIDE Pivotal Phase 2/3 clinical trial in desmoid tumors at the Connective Tissue Oncology Society (CTOS) 2022 Annual Meeting, taking place in-person November 16-19 in Vancouver, Canada (Press release, Ayala Pharmaceuticals, NOV 17, 2022, View Source [SID1234624193]).

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The ongoing RINGSIDE Pivotal Phase 2/3 clinical trial is evaluating the investigational new drug AL102, a potent, selective, oral gamma-secretase inhibitor. Positive interim results from the Phase 2 segment of this study were previously presented at ESMO (Free ESMO Whitepaper) 2022.

"We are pleased to update the positive interim data from RINGSIDE with the oncology community at this year’s CTOS meeting, which is the largest gathering of connective tissue oncologists worldwide," said Roni Mamluk, PhD, President and CEO of Ayala. "This poster highlights the efficacy demonstrated at the 1.2 mg dose that was selected for the Phase 3 segment of the study, with responses seen as early as 16 weeks that deepened over time. AL102 was generally well tolerated with a manageable safety profile."

Details of the poster presentation are as follows:

Abstract Title: Initial Results of RINGSIDE, a Phase 2/3 Trial of AL102 for the Treatment of Desmoid Tumors
Abstract Number: 2206585
Session Title: Sarcoma of the Year: Desmoid Fibromatosis
Session Date and Time: Thursday, November 17, 2022, 5 PM-7 PM PST
Poster Highlights:

Desmoid tumor is an invasive proliferative disease of the connective tissue characterized by a variable and often unpredictable clinical course with no FDA-approved therapies.
AL102 is a potent, orally available, selective gamma-secretase inhibitor being evaluated in the RINGSIDE Pivotal Phase 2/3 trial in desmoid tumors.
The Phase 2 segment of the study enrolled 42 patients which were dosed in AL102 monotherapy cohorts of 1.2 mg (daily), 2mg (2 days on, 5 days off), or 4mg (2 days on, 5 days off).
The activity of AL102 was measured by the change in tumor volume (central MRI readings) and response (per RECIST 1.1) as determined by blinded independent central review. At the data cut-off (July 14, 2022), 28 patients were evaluable for tumor volume and 29 were evaluable for RECIST with a scan at baseline and at least one additional scan at week 16.
12 patients had at least 2 MRI scans at data cut-off and were evaluable for efficacy.
First partial response (PR) was observed at week 16 and three additional PRs were observed over the follow-up period: two at week 28 and one at week 40.
3 out of 4 PRs were observed at the 1.2 mg once-daily dose that was selected for the Phase 3 segment of the study.
AL102 was generally well tolerated at all doses, with low rates of grade 3, and no grade 4 or 5 adverse events. Adverse events were consistent with mechanism of action of GSIs.
Adverse events leading to discontinuation were all Grade 1 – 3 and occurred within 3 months of treatment initiation
Adverse events related to ovarian dysfunction was observed in 22% of women of childbearing potential (N=23), and were all Grade 1 or 2
1.2 mg once daily was selected as the dose to advance into the Phase 3 portion of RINGSIDE.
Enrolment has begun in the Phase 3 segment of RINGSIDE, the randomized portion of the study Patients are also being enrolled in an open-label extension study.

About the RINGSIDE study

The RINGSIDE pivotal Phase 2/3 study is a randomized global multi-center trial. The Phase 2 segment of the study evaluated the efficacy, safety, tolerability, and tumor volume by MRI after 16 weeks of AL102 in patients with desmoid tumors. It enrolled 42 patients and evaluated 3 doses of AL102. Patients who participated in the Phase 2 segment of the study are eligible to enroll into an open-label extension study at the selected dose of 1.2 mg daily, and long-term efficacy and safety will be monitored.

The Phase 3 segment of the study has been initiated. This is a double-blind, placebo-controlled segment enrolling up to 156 patients with progressive disease that compares AL102 at 1.2 mg once daily to placebo. The primary endpoint for the Phase 3 segment is progression-free survival (PFS), with secondary endpoints including objective response rate (ORR), duration of response (DOR), tumor volume reduction, and patient-reported Quality of Life (QOL) measures. For more information on the RINGSIDE Phase 2/3 study with AL102 for the treatment of desmoid tumors, please visit ClinicalTrials.gov and reference Identifier NCT04871282 (RINGSIDE).

About Desmoid Tumors

Desmoid tumors also called aggressive fibromatosis or desmoid-type fibromatosis, are rare connective tissue tumors that typically arise in the upper and lower extremities, abdominal wall, head and neck area, mesenteric root, and chest wall with the potential to arise in additional parts of the body. Desmoid tumors do not metastasize, but often aggressively infiltrate neurovascular structures and vital organs. People living with desmoid tumors are often limited in their daily life due to chronic pain, functional deficits, general decrease in their quality of life and organ dysfunction. Desmoid tumors have an annual incidence of approximately 1,700 patients in the United States and typically occur in patients between the ages of 15 and 60 years. They are most commonly diagnosed in young adults between 30-40 years of age and are more prevalent in females. Today, surgery is no longer regarded as the cornerstone treatment of desmoid tumors due to a high rate of recurrence post-surgery and there are currently no FDA-approved systemic therapies for the treatment of unresectable, recurrent, or progressive desmoid tumors.

On November 17, 2022 Alloy Therapeutics, a biotechnology ecosystem company, reported an antibody discovery collaboration spanning multiple precision immuno-oncology programs for Normunity, a biotech company that recently announced its $65 million Series A financing (Press release, Alloy Therapeutics, NOV 17, 2022, View Source [SID1234624192]). The collaboration will support the advancement of Normunity’s immune normalizers, antibody therapies designed to target novel mechanisms that free the body’s normal immunity to fight cancer, which are conceived through a unique biotech-academic collaboration with a renowned immuno-oncology university research lab.

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Alloy democratizes access to tools, technologies, and services that are foundational for discovering and developing therapeutic biologics and has partnered with more than 130 discovery teams across academia, biotech, and large biopharma organizations. Through its discovery services offering, Alloy conducts high-touch, bespoke therapeutic discovery campaigns against partners’ targets of interest.

"Our partnership reflects an exciting opportunity to pair Normunity’s insights in immune disruption and cancer disease biology with Alloy’s world-class antibody discovery expertise," said Normunity Chief Scientific Officer William LaRochelle, PhD. "We value Alloy’s collaborative approach and look forward to working together to advance the best therapeutic antibodies to target mechanisms discovered through Normunity’s platforms."

The collaboration between Alloy and Normunity is leveraging Alloy’s high velocity antibody discovery services offering, Daedamab, which takes a sequencing-first approach to antibody discovery that reduces discovery timelines without sacrificing quality. The Daedamab team is based in Alloy’s research facility in Athens, GA, and its workflow comprises the ATX-Gx, Alloy’s proprietary mice platform for human therapeutic antibody discovery, in addition to robust B cell isolation, next generation sequencing, cloning-free expression and a high throughput screening process—all supported by a rich informatics engine.

"We are very excited to work with Normunity on its set of unique immuno-oncology targets using our high velocity NGS-based antibody discovery methods leveraging the ATX-Gx platform," said Richard Shimkets, PhD, SVP of Genetics and New Technologies at Alloy Therapeutics and CEO of the Daedamab site. "This relationship is emblematic of Alloy’s expertise in deploying the right technologies and processes to find our partners the best therapeutic antibodies against the novel targets they bring us."

Normunity is advancing into the clinic with programs that target mechanisms that drive the exclusion of T cells into immune-sensitive tumors and aim to deliver an active and effective immune system into cold tumors.

About Daedamab

Alloy’s Daedamab discovery service offers a novel, fast, powerful sequence-first approach to finding and making the best antibodies. The team is based in Athens, GA and supports Alloy collaborators with complete antibody discovery services, antibody sequencing of customer-provided material, expression and testing of customer-provided antibody sequences, humanization, and optimization services.

On November 17, 2022 Vivesto reported that Interim report for the period January 1, 2022 – September 30, 2022 (Press release, Vivesto, NOV 17, 2022, View Source [SID1234624190])

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SIGNIFICANT EVENTS DURING THE THIRD QUARTER
In July Christer Nordstedt was appointed acting CEO.
In July Vivesto announced that the company has decided to wind down its activities in Russia following the Russian invasion of Ukraine, ongoing hostilities and international sanctions. The wind down of Vivesto’s activities in Russia means that a write down of SEK 44.6 million is carried out during the third quarter of 2022, equal to the net book value of the capitalized development costs for Paclical after amortization as of June 30, 2022.
In August, Vivesto’s and Elevar’s partner Inceptua began the commercial launch of Apealea in Germany.

SIGNIFICANT EVENTS AFTER THE REPORTING PERIOD
In November Vivesto announced that the acting CEO Christer Nordstedt had resigned from his position in order to assume a new role outside of the company. Christer Nordstedt will remain as senior advisor to Vivesto on a consultancy basis within R&D.

THIRD QUARTER: JULY 1, 2022 – SEPTEMBER 30, 2022
Consolidated net sales amounted to TSEK 1,015 (11,920)
Operating profit/loss was TSEK 71,318 (-29,572)
Write-down of development costs attributable to Russia TSEK -44,624 (0)
Operating profit/loss adjusted for write-down of development costs attributable to Russia
TSEK -26,694 (-29,572), a decrease of SEK 2,878

Net profit/loss after tax amounted to TSEK -71,682 (-30,987)
Earnings per share amounted to SEK -0.14 (-0.07)
THE PERIOD: JANUARY 1, 2022 – SEPTEMBER 30, 2022
Consolidated net sales amounted to TSEK 1,015 (16,553)
Operating profit/loss was TSEK -133,970 (-126,579)
Write-down of development costs attributable to Russia TSEK -44,624 (0)
Operating profit/loss adjusted for write-down of development costs attributable to Russia TSEK -89,346 (-126 579), a decrease of SEK 37,233
Net profit/loss after tax amounted to TSEK -136,653 (-129,873)
Earnings per share amounted to SEK -0.28 (-0.29)
Short-term investments, cash and cash equivalents amounted to TSEK 164,241 (149,677)
Equity/assets ratio was 95% (80%)

Invitation to presentation of Vivesto’s Q3 report
Vivesto will hold a conference call and an online presentation of the Q3 report on November 17, 2022, at 10.00 am CET. The call will be hosted by Acting CEO Christer Nordstedt and Acting CFO Robert Maiorana. The presentation will be in English and followed by a question-and-answer session. The conference call will be broadcast live on the web via the link:
View Source

On November 16, 2022 Greywolf Therapeutics, a biotechnology company focused on generating entirely novel anti-tumour immune responses through targeted cancer neoantigen creation, reported it has entered into a clinical supply agreement with Regeneron for their PD-1 inhibitor Libtayo (cemiplimab) (Press release, Grey Wolf Therapeutics, NOV 16, 2022, View Source [SID1234650154]). The agreement relates to Greywolf’s planned Phase 1/2 clinical trial evaluating the safety, tolerability and efficacy of their lead development candidate GRWD5769 (an investigational first-in-class ERAP1 inhibitor), including in combination with Libtayo, in a range of solid tumour types. The study is expected to begin in the first half of 2023.

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In both the GRWD5769 monotherapy and GRWD5769/Libtayo combination modules of the trial, a particular focus will be on patients with virally associated solid tumours, such as head and neck squamous cell carcinoma, cervical cancer, and hepatocellular carcinoma as Greywolf’s analysis of patient data suggests these could be particularly sensitive to GRWD5769.

"GRWD5769 is a first-in-class ERAP1 inhibitor, designed to upregulate the generation of novel neoantigens, and mobilise an entirely novel T cell response against tumours, and in so doing overcome the challenges of T cell exhaustion. Based on this unique mechanism, we believe this compound holds great promise as a monotherapy, and we’re excited to evaluate our approach in the clinic where there is a particularly strong rationale for observing striking effects in patients with virally associated cancers." said Peter Joyce, Ph.D., chief executive officer of Greywolf Therapeutics. "At the same time, we believe that this innovative approach to attacking cancer also has great potential to synergistically improve outcomes when used in rational combination with other anti-cancer agents, particularly immune checkpoint inhibitors. As such, we are looking forward to the opportunity to assess GRWD5769 in combination with Regeneron’s Libtayo. Their continued investment in immuno-oncology innovation is clearly aligned with our first in class approach to cancer immunotherapy and we are delighted to be working with them as we progress into the clinic".