On March 23, 2023 Alpine Immune Sciences, Inc. (NASDAQ: ALPN), a leading clinical-stage immunotherapy company focused on developing innovative treatments for autoimmune and inflammatory diseases, reported a corporate update and reported financial results for the fourth quarter ended December 31, 2022 (Press release, Alpine Immune Sciences, MAR 23, 2023, View Source [SID1234629233]).

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"With the recent initiation of the RUBY-3 study in autoimmune glomerulonephritis and the imminent initiation of the RUBY-4 study in autoimmune cytopenias, 2023 is on track to be a pivotal year for Alpine and povetacicept, a potential best-in-class dual BAFF/APRIL inhibitor which we are developing for multiple autoantibody-related diseases. We look forward to sharing updates on both studies anticipated by the end of the year," said Mitchell H. Gold, MD, Executive Chairman and Chief Executive Officer of Alpine. "Our strong balance sheet and povetacicept’s promising preclinical and phase 1 healthy volunteer data, in addition to a convenient once every four-week subcutaneous dosing regimen, enables us to advance a robust development plan which has the potential to bring a meaningful new therapeutic option for patients living with multiple different autoimmune or inflammatory diseases."

"We are thrilled to be part of povetacicept’s RUBY-3 study for autoimmune glomerulonephritis, especially IgA nephropathy. Povetacicept looks to be the first true dual inhibitor of both the BAFF and APRIL cytokines with the added potential advantage of its unique, convenient dose regimen of subcutaneous administration every four weeks," said James Tumlin, MD, Founder and Medical Director of the NephroNet Clinical Trials Consortium, Professor of Medicine at Emory University School of Medicine, and principal investigator for the RUBY-3 study. "Our site has had a strong patient interest in participating in this trial given the significant unmet need for glomerulonephritis which can lead to renal failure and the need for dialysis or transplantation if untreated. We look forward to continuing to work with the Alpine team to study povetacicept’s potential to be an important new and potent disease-modifying therapy."

Fourth Quarter 2022 and Recent Pipeline and Corporate Updates

Povetacicept (ALPN-303)

RUBY-3, an open-label basket study in autoimmune glomerulonephritis, including IgA nephropathy, lupus nephritis and primary membranous nephropathy, recently initiated enrollment.
RUBY-4, an open-label basket study in autoimmune cytopenias, including immune thrombocytopenia, warm autoimmune hemolytic anemia, and cold agglutinin disease, is anticipated to begin enrollment in the second quarter.
The Company plans to launch RUBY-2, a placebo-controlled, dose-ranging, randomized phase 2 study in systemic lupus erythematosus in mid-2024, based on enabling data from the RUBY-3 and RUBY-4 studies.
Key preclinical data on povetacicept — demonstrating differentiation from wild-type TACI-Igs, BAFF- or APRIL-only inhibitors and anti-CD20 depletion, as well as efficacy in mouse models of lupus — were published in the peer-reviewed journal Arthritis & Rheumatology (View Publication).
The Company presented multiple oral and poster presentations on povetacicept at recent scientific conferences, including an ePoster and oral presentation at the American Academy of Dermatology Annual Meeting on March 18th (Full List of Company Publications and Presentations).
Corporate

The Company recently announced that it had entered into a strategic collaboration with Truveta to use Truveta Studio to help rapidly identify and enroll participants in Alpine’s clinical studies for povetacicept, including the RUBY-3 study in autoimmune glomerulonephritis and RUBY-4 study in autoimmune cytopenias. Truveta’s databases are updated daily from its 28 health system members which include more than 20,000 clinics and 700 hospitals from all 50 states and represent 16% of the covered lives in the United States.
The Company ended the year with $273.4 million in cash, cash equivalents, restricted cash, and investments as of December 31, 2022, which the Company anticipates should be sufficient to fund its planned operations through 2025.
Fourth Quarter and Full Year 2022 Financial Results

As of December 31, 2022, Alpine’s cash, cash equivalents, restricted cash and investments totaled $273.4 million. The Company recorded net losses of $57.8 million and $50.3 million for the years ended December 31, 2022 and 2021, respectively.

Collaboration revenue for the quarter ended December 31, 2022 was $2.8 million compared to $4.5 million for the quarter ended December 31, 2021. The decrease primarily relates to lower revenue recognized under our collaboration with AbbVie partially offset by revenue recognized for services performed in connection with our collaboration with Horizon, which was executed in late 2021.

Research and development expenses for the quarter ended December 31, 2022 were $18.8 million compared to $15.4 million for the quarter ended December 31, 2021. The increase was primarily attributable to higher personnel-related expenses due to increased headcount to support our ongoing and planned clinical development programs.

General and administrative expenses for the quarter ended December 31, 2022 were $4.4 million compared to $4.5 million for the quarter ended December 31, 2021.

The Company recorded net losses of $18.9 million and $15.2 million for the quarters ended December 31, 2022 and 2021, respectively.

Conference Call and Webcast Information

The link to the webcast will be available in the investor relations section of the Company’s website at View Source and a replay will be available on the Company’s website for 90 days following the live event.

About Povetacicept (ALPN-303)

Povetacicept (ALPN-303) is a dual antagonist of the BAFF (B cell activating factor) and APRIL (a proliferation inducing ligand) cytokines, which play key roles in the activation and survival of B cells, particularly antibody-secreting cells. Based upon an engineered TACI (transmembrane activator and CAML interactor) domain, povetacicept exhibits greater potency in preclinical studies versus wild-type TACI-based comparators, as well as other inhibitors of BAFF and/or APRIL alone. Povetacicept is in development for multiple B cell and/or autoantibody-related diseases, such as systemic lupus erythematosus, autoimmune glomerulonephritis, and autoimmune cytopenias.

On March 23, 2023 AstraZeneca’s Calquence (acalabrutinib), a next generation, selective Bruton’s tyrosine kinase (BTK) inhibitor,reported that it has been conditionally approved in China for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy (Press release, AstraZeneca, MAR 23, 2023, View Source [SID1234629198]). This is the first approved indication for Calquence in China.

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The conditional approval by the National Medical Products Administration (NMPA) was based on positive results from two clinical trials, including the ACE-LY-004 global Phase II trial in adults with relapsed or refractory MCL and a Phase I/ II trial in Chinese patients with relapsed or refractory MCL and other B-cell malignancies.1,2 Continued approval for this indication may be contingent upon verification of ongoing randomised controlled confirmatory trials.

MCL is typically an aggressive, rare form of non-Hodgkin lymphoma (NHL) that accounts for between 2-6% of all patients diagnosed with NHL in China. Patients are generally diagnosed around 60 years of age, often at later stages of the disease.3

Jun Zhu, Chief Physician, Department of Lymphatic Oncology, Peking University Cancer Hospital, Beijing, said: "Mantle cell lymphoma progresses rapidly and responds poorly to conventional treatment such as immunochemotherapy. Before the emergence of BTK inhibitors, there were few satisfactory treatment options for patients. The next-generation BTK inhibitor Calquence has higher target selectivity, fewer side effects, and a higher response rate compared to currently available treatments. This approval of Calquence in China can provide a new treatment option which can better benefit patients with this disease."

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: "This approval for Calquence offers people living with mantle cell lymphoma in China an effective and tolerable new treatment option to help control their disease. As the first approval in China for Calquence, it is also an exciting step forward for AstraZeneca in blood cancers, enabling us to help more patients across the globe gain access to innovative treatments."

Results from the ACE-LY-004 Phase II trial showed at a median follow up of 15.2 months, investigator-assessed overall response rate (ORR) with Calquence was 80.6% (95% confidence interval [CI] 72.6-87.2), with a complete response (CR) achieved in 39.5% of patients with relapsed or refractory MCL (95% CI 30.9-48.7).1 Longer-term follow-up data showed at 38.1 months, patients treated with Calquence remained progression-free for a median of 22 months, with median overall survival (OS) of 59.2 months (95% CI 36.5-NE).4

Additionally, results from a Phase I/II trial conducted in China showed Calquence achieved a 82.4% ORR, with a CR achieved in 35.3% of patients with MCL based on a blinded independent central-review (BICR) analysis (95% CI 65.5-93.2). Calquence reduced the risk of disease progression or death by 51.5% (95% CI 33.3-67.0) at 12 months, with an estimated duration of response (DOR) of 65.5% (95% CI 66.6-93.3). The median DOR was not reached.2

The safety and tolerability of Calquence in these trials was consistent with that observed in previous clinical trials.1,2,4

Calquence is approved for the treatment of chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL) in the US and Japan and is approved for the treatment of CLL in the EU and in several other countries worldwide in the treatment-naïve and relapsed or refractory settings. Calquence is also approved in the US and several other countries for the treatment of adult patients with MCL who have received at least one prior therapy. Calquence is not currently approved for the treatment of MCL in Japan or the EU.

Notes

Mantle cell lymphoma (MCL)
MCL is a rare B-cell malignancy subtype and is typically clinically aggressive with a poor prognosis.3 The epidemiology of MCL in Asia is not well documented, with few published datasets describing the incidence and outcomes.3 MCL accounts for between 2-6% of all patients diagnosed with NHL China.3 Patients are generally diagnosed around 60 years of age and often at later stages of disease (Stage III or IV).3

ACE-LY-004
ACE-LY-004 is an open-label, single-arm Phase II clinical trial evaluating Calquence in adult patients with relapsed or refractory MCL.5 Patients in the trial were adults with MCL and an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2 or lower who had relapsed or were refractory to 1-5 prior therapies, had no prior BTK/BCL-2 inhibitor exposure, and did not require warfarin/vitamin K antagonists. Patients received oral Calquence 100mg twice-daily until progressive disease or toxicity. ORR (investigator-assessed partial response or better per Lugano classification), DOR, progression-free survival (PFS), OS and safety were assessed.1

Phase I/II trial in Chinese patients
The Phase I/II trial is an open-label, multicentre clinical trial evaluating pharmacokinetics, safety and efficacy of Calquence in adult Chinese patients with relapsed or refractory MCL and other advanced B-cell malignancies.2 In Phase I, patients with relapsed or refractory B-cell malignancies received a single dose of Calquence 100mg orally followed by a two-day washout period and subsequent treatment with Calquence 100mg orally twice daily in 28-day cycles, until progressive disease (PD) or treatment discontinuation (TD) for any other reason. In Phase II, patients with relapsed or refractory MCL and ECOG status of 2 or lower received Calquence 100mg orally twice daily in 28-day cycles until PD or TD. The primary efficacy endpoint was ORR per Lugano classification for NHL assessed by BICR. Secondary endpoints were investigator-assessed ORR, BICR- and investigator-assessed time to response, DOR, PFS, OS and adverse events. 2

Calquence
Calquence (acalabrutinib) is a next-generation, selective inhibitor of BTK. Calquence binds covalently to BTK, thereby inhibiting its activity.6 In B cells, BTK signalling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis and adhesion.

Calquence is approved for the treatment of CLL and SLL in the US, approved for CLL in the EU and many other countries worldwide and approved in Japan for relapsed or refractory CLL and SLL.

As part of an extensive clinical development programme, AstraZeneca is currently evaluating Calquence in more than 20 company-sponsored clinical trials. Calquence is being evaluated for the treatment of multiple B-cell blood cancers, including CLL, MCL, diffuse large B-cell lymphoma, Waldenström’s macroglobulinaemia, marginal zone lymphoma and other haematologic malignancies.

AstraZeneca in haematology
AstraZeneca is pushing the boundaries of science to redefine care in haematology. We have expanded our commitment to patients with haematologic conditions, not only in oncology but also in rare diseases with the acquisition of Alexion, allowing us to reach more patients with high unmet needs. By applying our deep understanding of blood cancers, leveraging our strength in solid tumour oncology and delivering on Alexion’s pioneering legacy in complement science to provide innovative medicines for rare diseases, we are pursuing the end-to-end development of novel therapies designed to target underlying drivers of disease.

By targeting haematologic conditions with high unmet medical needs, we aim to deliver innovative medicines and approaches to improve patient outcomes. Our goal is to help transform the lives of patients living with malignant, rare and other related haematologic diseases, shaped by insights from patients, caregivers and physicians to have the most meaningful impact.

AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

On March 23, 2023 Immutep Limited (ASX: IMM; NASDAQ: IMMP), a clinical-stage biotechnology company developing novel LAG-3 immunotherapies for cancer and autoimmune disease, reported that new data evaluating eftilagimod alpha in combination with pembrolizumab from Part B of the TACTI-002 Phase II trial in 2nd line PD-X refractory non-small cell lung cancer (NSCLC) patients has been accepted for a Mini Oral presentation at ESMO (Free ESMO Whitepaper)’s European Lung Cancer Congress (ELCC) 2023 taking place in Copenhagen, Denmark and virtually from 29 March to 1 April 2023 (Press release, Immutep, MAR 23, 2023, View Source [SID1234629197]).

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The PD-X refractory, NSCLC patients in Part B of the TACTI-002 Phase II trial represent a difficult-to-treat patient population. All enrolled patients (N=36) had confirmed progression (i.e., two consecutive scans) after standard of care 1st line treatment with anti-PD-X therapy including a majority that received anti-PD-X therapy and chemotherapy. Additionally, most patients had low or negative PD-L1 expression.

TACTI-002 (Part B) Abstract (#11MO)
Title: Final data from a phase II study (TACTI-002) of eftilagimod alpha (soluble LAG-3) & pembrolizumab 2nd line metastatic NSCLC patients resistant to PD-1/PD-L1 inhibitors
Presentation session: Mini Oral
Presenter: Margarita Majem, MD, PhD, Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau
Lecture Time: 31 March 2023, 08:25-08:30AM

The abstract (#11MO) will be available here on the ELCC 2023 website. The related Mini Oral Presentation with new and updated final data that are not part of the abstract will made available on 31 March 2023 at 08:25AM, CEST and will subsequently be posted on the Posters & Publications section of Immutep’s website.

On March 22, 2023 EpiBiologics, a biotechnology company building a next-generation antibody-based protein degradation platform for membrane and extracellular drug targets, reported the company launched with $50 million in Series A funding (Press release, EpiBiologics, MAR 22, 2023, View Source [SID1234643975]). The funding was co-led by Mubadala Capital and Polaris Partners, with participation from Vivo Capital and GV. The company’s technology platform is based on the scientific work of EpiBiologics’ co-founder and renowned antibody engineer Dr. Jim Wells of the University of California, San Francisco (UCSF), and the platform intellectual property has been exclusively licensed from UCSF.

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Protein degradation technologies are of high interest to the medical community because of their potential to attack disease targets that have been historically difficult to drug. However, companies pursuing these approaches have focused primarily on intracellular proteins. EpiBiologics’ proprietary EpiTAC platform expands the targeted protein degradation landscape to the extracellular space, enabling the company to target both membrane proteins and secreted proteins through the use of genetically encoded bifunctional antibodies. As reported in Nature Biotechnology and the Journal of the American Chemical Society, the Wells Lab at UCSF demonstrated that membrane E3 ligases and cytokine receptors could be leveraged as cell surface ligands to internalize and degrade a number of membrane or extracellular drug targets. EpiBiologics has now expanded the platform and built an atlas of tissue-specific degrader antibodies to target proteins for new treatments for a range of diseases, including cancer, immunology and neuro-related conditions.

"Our vision has been to build EpiBiologics to be the leading company in the extracellular degradation space," said Dr. Rami Hannoush, co-founder, interim CEO and President of EpiBiologics, who has also served as Chief Scientific Officer of the company since its inception. "Since launching the company, the team at EpiBiologics has been able to further validate and industrialize the EpiTAC platform, creating a fit-for-purpose atlas of degraders. The current financing will enable us to expand and validate the platform, advance our pipeline of drug candidates, and further build our talented team of scientists and protein engineers."

To strengthen their leadership and support their expansion, EpiBiologics also announced the appointment of Shyra Gardai as its incoming Chief Scientific Officer. With over 20 years of scientific and pre-clinical drug development experience across multiple key therapeutic areas, Dr. Gardai has served in roles of increasing responsibilities in the biotechnology industry, including most recently as Vice President of Therapeutic Discovery Research at Seagen.

"I’m looking forward to working with the talented team at EpiBiologics to develop innovative therapeutics for hard-to-treat diseases," said Dr. Gardai, CSO of EpiBiologics. "Leveraging EpiBiologics’ technology platform we are taking a novel approach to degrade disease-causing targets that evade existing therapeutic approaches."

"EpiBiologics represents a key example of our company formation efforts, where we worked hand-in-hand with the founding scientists to build the company from the ground up. We have a strong conviction in the transformative potential of EpiBiologics to advance the field of protein degradation," said Alaa Halawa, Executive Director and Head of the U.S. Ventures business at Mubadala Capital.

"We believe EpiBiologics’ core technology has the potential to greatly expand the scope of therapeutically relevant targets that can be successfully drugged through degradation, and we are excited to support their growing team of talented scientists, drug developers and industry leaders," said Alexandra Cantley, Partner at Polaris Partners.

On March 22, 2023 WuXi Biologics reported its 2022 annual results (Filing, 3 mnth, DEC 31, WuXi Biologics, 2022, MAR 22, 2023, View Source [SID1234630448]).

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