On March 23, 2023 Applied Therapeutics, Inc. (Nasdaq: APLT), a clinical-stage biopharmaceutical company developing a pipeline of novel drug candidates against validated molecular targets in indications of high unmet medical need, reported financial results for the fourth quarter and full year ended December 31, 2022 (Press release, Applied Therapeutics, MAR 23, 2023, View Source [SID1234629235]).

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"We are pleased with the clinical progress in 2022 across all three of our registrational Phase 3 programs, and we look forward to the data readouts in the year ahead," said Shoshana Shendelman, PhD, Founder and CEO of Applied Therapeutics. "Our recent deal with Advanz Pharma highlights our ability to realize value in our clinical programs, and we continue to evaluate other potential opportunities for value recognition."

Recent Highlights

· Announced Positive Sorbitol Reduction Data from the Ongoing Phase 3 INSPIRE Trial in Sorbitol Dehydrogenase (SORD) Deficiency. In February 2023, the Company announced positive sorbitol reduction data from the ongoing global Phase 3 INSPIRE trial. The INSPIRE trial is a Phase 3 double-blind placebo-controlled registrational study evaluating the effect of once-daily oral AT-007 in approximately 50 patients age 16-55 with SORD Deficiency in the US and Europe. SORD Deficiency (also called SORD Neuropathy or CMT-SORD) is a debilitating hereditary axonal neuropathy caused by mutations in the Sorbitol Dehydrogenase gene, leading to an inability to metabolize the sugar sorbitol, and resulting in accumulation of high levels of toxic sorbitol, which causes motor neuron degeneration and loss of mobility and motility. AT-007 (govorestat) is a central nervous system penetrant Aldose Reductase Inhibitor, which blocks conversion of glucose to sorbitol, and has previously been shown to reduce sorbitol levels in an open-label pilot study in patients with SORD Deficiency. In a pre-specified interim analysis of the ongoing Phase 3 INSPIRE trial, AT-007 reduced sorbitol levels by a mean of approximately 52% (or approximately 16,000ng/ml) over 90 days of treatment (p<0.001 vs. placebo) in patients with SORD Deficiency.

· Announced Partnership with Advanz Pharma for Commercialization of Govorestat in Europe. In January 2023, the Company announced a partnership with Advanz Pharma, a pharmaceutical company with a strategic focus on commercialization of specialty, hospital, and rare disease medicines, for commercialization of govorestat in Europe. Under the terms of the agreement, the Company will receive certain near-term development milestone payments upon clinical trial completion and marketing authorization in Europe as well as commercial sales milestones, which in the aggregate amount to over €130 million, including €10 million upfront provided upon signing. The Company will receive royalties on any future net sales of govorestat in Europe of 20% and will continue to be responsible for the development, manufacturing and supply of govorestat

Financial Results

· Cash and cash equivalents and short-term investments totaled $30.6 million as of December 31, 2022, compared with $80.8 million at December 31, 2021.

· Research and development expenses for the year ended December 31, 2022 were $55.6 million, compared to $62.6 million for the year ended December 31, 2021. The decrease of approximately $6.9 million was primarily related to a decrease in drug manufacturing and formulation expenses of $11.0 million primarily related to the completion and release of AT-001 and AT-007 drug product batches in the year ended December 31, 2021 and a decrease of regulatory and other expenses of $0.6 million primarily related to the University of Miami license fees recognized during the year ended December 31, 2021, which was offset by an increase in clinical and pre-clinical expense of $2.6 million, primarily related to the progression of the SORD Phase 2/3 registrational study, progression of the AT-007 ACTION-Galactosemia long-term extension adult study, and progression of the AT-007 ACTION-Galactosemia Kids pediatric registrational study; an increase in personnel expenses of $1.1 million due to the increase in headcount in support of our clinical program pipeline; and an increase in stock-based compensation of $0.9 million due to new stock option and restricted stock unit grants, offset by forfeitures of stock option and restricted stock unit grants.

· General and administrative expenses were $27.3 million for the year ended December 31, 2022, compared to $43.0 million for the year ended December 31, 2021. The decrease of approximately $15.7 million was primarily related to a decrease of $9.1 million related to decreased spend for commercial operations; a decrease in personnel expenses of $1.1 million and a decrease in stock-based compensation of $2.9 million due to a decrease in headcount; a decrease of insurance expenses of $0.7 million related to decreased directors and officers liability insurance costs; and a decrease in other expenses of $2.4 million, primarily relating to decreased costs of other office expenses, which was offset by an increase in professional and legal fees of $0.5 million due to higher external legal fees.

· Net loss for the year ended December 31, 2022 was $82.5 million, or $2.18 per basic and diluted common share, compared to a net loss of $105.6 million, or $4.12 per basic and diluted common share, for the year ended December 31, 2021.

On March 23, 2023 Anaveon, a clinical stage, immuno-oncology company, reported that it will present a poster on ANV600 at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 23rd Annual Meeting being held from Friday, April 14, 2023, to Wednesday, April 19, 2023, in Orlando, Florida (Press release, Anaveon, MAR 23, 2023, https://anaveon.com/anaveon-announces-presentation-of-a-novel-development-compound-at-the-2023-american-association-for-cancer-research-annual-meeting/ [SID1234629234]).

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ANV600 is a novel bispecific compound, comprising an anti-IL-2 antibody/IL-2 fusion protein and a proprietary hPD-1 binding moiety for specific delivery of IL-2 to tumor antigen experienced PD-1+ T cells. ANV600 treatment leads to a dose-dependent increase of intratumoral, stem-like and cytotoxic PD-1+T cells in mice harboring B16F10 and MC38 subcutaneous tumors and markedly retards tumor growth.

"ANV600 is a powerful, new, targeted therapeutic with the potential to extend the benefits of IL-2 therapies to less immunogenic tumors," said Christoph Huber, Chief Scientific Officer of Anaveon. "We plan to initiate clinical studies in early 2024 to determine the therapeutic benefit in patients."

The abstract will be published on Friday, March 31 on an online-only Proceedings supplement to the AACR (Free AACR Whitepaper) journal Cancer Research. The accompanying poster will be on display on Anaveon’s website on April 14, 12:00 pm EDT.

Details of the poster presentation:

Tuesday, April 18, 9:00 am – 12:30 pm EDT, Poster #4127

Title: ANV600 is a potent, cis-signaling, non-alpha IL-2 agonist which efficiently expands intratumoral stem-like CD8 T cells

Authors: P. Murer, U. Salazar, N. Egli, L. Petersen, P. Neubert, K. Richter, Ch. Stocker, A. Rau, A. Katopodis and Ch. Huber

Anaveon is developing selective cytokine receptor agonists with the potential to therapeutically enhance a patient’s immune system to respond to tumors. ANV419, currently in Ph II studies in multiple cancer indications, is designed to preferentially signal through the IL-2 beta/gamma receptor resulting in strong proliferation of effector cells in patients. The follow-on compound, ANV600, targets the selective IL-2 receptor moiety to intratumoral effector cells and may have therapeutic benefit in less immunogenic tumors. These novel types of therapeutics, if approved, could potentially have a wide utility in oncology, including in combination with checkpoint inhibitors, cell therapies, vaccines, and radiotherapy.

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.