Lutikizumab Showed Positive Results in a Phase II Trial of Adults with Moderate to Severe Hidradenitis Suppurativa as Program Advances to Phase III

AbbVie has reported the results of Phase II trials indicating that adults experiencing moderate to severe hidradenitis suppurativa, and who had previously not responded to anti-TNF therapy, exhibited higher rates of response (59.5% with a nominal p-value of 0.027 for the 300 mg every other week dosage, and 48.7% with a nominal p-value of 0.197 for the 300 mg weekly dosage) compared to those who received a placebo (35%). The primary endpoint, achieving hidradenitis suppurativa Clinical Response (HiSCR 50) at week 16, was met. With these findings, AbbVie intends to advance the clinical development of lutikizumab in hidradenitis suppurativa to Phase II. Lutikizumab, developed by AbbVie, is a dual-variable-domain interleukin (IL) 1α/1β antagonist currently under investigation. Research indicates an elevation of IL 1α and 1β in lesions associated with Hidradenitis Suppurativa.

Roopal Thakkar, M.D., senior vice president, chief medical officer, global therapeutics at AbbVie, expressed the company’s commitment to advancing research for new hidradenitis suppurativa treatment options. Hidradenitis suppurativa affects a patient population that is often overlooked and underserved, leading to significant suffering. Dr. Thakkar highlighted that the recent findings on lutikizumab in adults with moderate to severe hidradenitis suppurativa contribute to the understanding of its potential use. AbbVie, drawing on over 25 years of expertise in immune-mediated diseases, plans to leverage these results to progress lutikizumab through Phase III of its clinical program for hidradenitis suppurativa.

This research spanned 16 weeks and constituted a Phase II investigation employing a randomized, double-blind, parallel-group, placebo-controlled, dose-ranging, and multicenter design. The objective was to assess the safety and effectiveness of lutikizumab in 153 adult patients facing moderate to severe Hidradenitis Suppurativa, who had previously experienced unsuccessful anti-TNF therapy. A significant majority of participants (70.6%) exhibited severe baseline Hurley Stage 3 disease, characterized by extensive HS manifestations involving scarring, lesions, and sinus tracts. At the outset, patients were randomly assigned to receive one of three subcutaneous doses of lutikizumab (100 mg every other week, 300 mg every other week, or 300 mg every week) or a placebo. The primary endpoint of the study was the attainment of HiSCR 50 at week 16, with the secondary endpoint being the assessment of skin pain using the NRS30 scale at week 16, limited to subjects with a baseline NRS≥3.

Merck to Acquire Harpoon Therapeutics, Further Diversifying Oncology Pipeline

Merck, operating as MSD internationally, and Harpoon Therapeutics, Inc. have disclosed a definitive arrangement wherein Merck, via a subsidiary, will purchase Harpoon at $23.00 per share in cash, resulting in an estimated total equity value of $680 million. 

“At Merck, we are actively strengthening our oncology pipeline by strategically acquiring assets that align with our existing portfolio and push forward groundbreaking scientific advancements to meet the global needs of individuals affected by cancer,” stated Dr. Dean Y. Li, President of Merck Research Laboratories. “This collaboration underscores the ingenuity and dedication of the scientists and clinical development teams at Harpoon. We are eager to explore the potential of HPN328 in novel combinations with other candidates in our pipeline.”

Harpoon has created a range of innovative T-cell engagers utilizing their exclusive Tri-specific T-cell Activating Construct (TriTAC®) platform. This engineered protein technology aims to guide the patient’s immune cells toward eliminating tumor cells. Additionally, Harpoon has developed the ProTriTAC™ platform, which incorporates a prodrug concept into the TriTAC® platform. This results in a therapeutic T-cell engager designed to stay inactive until it reaches the tumor.

Julie Eastland, the President and CEO of Harpoon Therapeutics, expressed the company’s unwavering dedication to advancing cancer immunotherapy candidates for the betterment of patients. With Merck’s well-established leadership in oncology clinical development and a strong global commercial presence, Harpoon’s lead candidate, HPN328, is strategically positioned for future progress. Eastland acknowledged the remarkable contributions of the skilled and passionate Harpoon team over the past eight years, leveraging their research platform to create an innovative suite of candidates. She expressed gratitude to key stakeholders, including the Harpoon team, trial participants, physicians, and shareholders, for their ongoing support. The recognition of the significant potential in Harpoon’s pipeline by Merck is particularly pleasing to the company.

Harpoon’s primary candidate, HPN328, is a T-cell engager designed to target delta-like ligand 3 (DLL3), an inhibitory canonical Notch ligand that is prominently expressed in small cell lung cancer (SCLC) and neuroendocrine tumors. Currently undergoing assessment in a Phase I/II clinical trial, HPN328 is being investigated for its safety, tolerability, and pharmacokinetics when used as monotherapy in patients with advanced cancers characterized by DLL3 expression. The trial also explores the combination of HPN328 with atezolizumab in SCLC patients. In October 2023, Harpoon reported positive interim results related to tolerability and response for HPN328 in specific SCLC and neuroendocrine tumor patients.

Other potential pipeline options comprise HPN217, which focuses on B-cell maturation antigen (BCMA) and is presently undergoing Phase I clinical trials to address relapsed/refractory multiple myeloma. Additionally, there are several candidates in the preclinical stage, such as HPN601. This candidate is conditionally activated and aims at treating individuals with tumors expressing epithelial cell adhesion molecule (EpCAM).

Novo Nordisk Enters into Research Collaborations with Omega Therapeutics and Cellarity on Novel Treatment Approaches for Cardiometabolic Diseases

Novo Nordisk, along with Omega Therapeutics, Inc. and Cellarity Inc., have revealed individual research partnerships. The collaboration with Omega will utilize its exclusive platform technology to create an epigenomic controller aimed at improving metabolic activity, potentially offering a new avenue for addressing obesity. Meanwhile, the collaboration with Cellarity seeks to uncover new biological factors influencing MASH, using Cellarity’s platform to develop a small molecule therapy for this condition.

The initial two initiatives have been formally agreed upon within the collaborative framework between Flagship Pioneering and Novo Nordisk. These programs aim to utilize Flagship’s bioplatform companies to create innovative treatment methods for cardiometabolic diseases.”

This marks a crucial milestone in our collaboration with Flagship Pioneering. We anticipate progressing these research programs alongside Omega and Cellarity in the upcoming years, delving into innovative treatment approaches that hold the potential to significantly benefit individuals facing obesity or metabolic-associated fatty liver disease (MAFLD),” stated Marcus Schindler, Executive Vice President and Chief Scientific Officer at Novo Nordisk. “Novo Nordisk remains dedicated to advancing fresh treatment alternatives for those with cardiometabolic conditions. In pursuit of this goal, it is imperative to complement our internal research with external innovation and engage with partners leveraging cutting-edge technology. Both companies bring distinctive and inventive methods to the table, with Omega’s proficiency in controlled epigenomic modulation and Cellarity’s profound insights into integrating human data and artificial intelligence for the development of novel medicines.”

Abbisko Therapeutic Announces that EMA has Granted Orphan Drug Designation for its CSF-1R Inhibitor Pimicotinib ABSK021）

On January 9, 2024, Abbisko Therapeutics announced that its investigational CSF-1R inhibitor known as pimicotinib (ABSK021) received Orphan Drug Designation (ODD) from the European Medicines Agency (EMA). This designation specifically applies to the treatment of inoperable Tenosynovial Giant Cell Tumor (TGCT), signifying recognition and support for the development of this innovative therapeutic approach.

Pimicotinib stands as a novel, orally administered, remarkably selective, and potent small molecule CSF-1R inhibitor, developed autonomously by Abbisko Therapeutics. It has received Breakthrough Designation (BTD) and PRIME designation from regulatory bodies including China’s NMPA, the U.S. FDA, and the EMA. These designations recognize its potential for treating Tenosynovial Giant Cell Tumor (TGCT) patients who are not suitable for surgery. This study marks the pioneering global Phase III clinical trial for TGCT, conducted concurrently in China, the U.S., Canada, and Europe.

In the 1-year follow-up of Phase 1b trial focusing on Tenosynovial Giant Cell Tumor (TGCT), pimicotinib showcased an impressive Overall Response Rate (ORR) of 87.5% (28 out of 32 patients, including 3 complete responses) within the 50 mg once-daily cohort. These findings were presented at the 2023 CTOS (Connective Tissue Oncology Society) conference.

Pimicotinib has successfully concluded its Phase I dose-escalation trial in the United States. Moreover, in December of the same year, it received Fast Track Designation (FTD) from the U.S. FDA, signifying acknowledgment of its potential for treating unresectable TGCT.

Earlier in June 2023, pimicotinib received the Priority Medicines (PRIME) designation from the European Medicines Agency (EMA). This designation is granted to promising medicines targeting areas with significant unmet medical needs. Its primary objective is to accelerate the review process, facilitating the development and availability of such medications to patients who require them urgently. 

In December 2023, Abbisko engaged in a strategic agreement with Merck, granting Abbisko an exclusive license to commercialize pimicotinib for all indications across the Chinese mainland, Hong Kong, Macau, and Taiwan. Simultaneously, Merck secured an exclusive option for global commercial rights to pimicotinib, subject to prearranged terms and conditions.

As part of this licensing agreement, Abbisko is set to receive an initial one-time, non-refundable down payment of US$ 70 million. Should Merck decide to exercise its option for global commercialization, an additional fee will be paid to Abbisko. The total sum, including the upfront payment, the fee for exercising the option, and potential payments linked to development and commercialization milestones, is estimated to reach US$ 605.5 million. Additionally, Abbisko stands to gain double-digit percentage royalties on annual net sales of pimicotinib.

Abbisko is fervently investigating the broader potential of pimicotinib beyond Tenosynovial Giant Cell Tumor (TGCT). Their exploration encompasses various solid tumor types in clinical trials. They’ve secured approval from China’s NMPA to initiate Phase II clinical investigations targeting chronic graft-versus-host disease (cGVHD) and advanced pancreatic cancer using pimicotinib.

FDA Grants Soligenix “Fast Track” Designation for Dusquetide in the Treatment of Oral Lesions of Behçet’s Disease

On January 8, 2024, Soligenix, Inc. (Nasdaq: SNGX) announced that its SGX945 (dusquetide) development program for the treatment of oral lesions of Behçet’s Disease has received “Fast Track” designation from the US FDA.

Dusquetide, the active component found in SGX945 (used for Behçet’s disease) and SGX942 (for oral mucositis), belongs to a novel category of synthetic peptides known as innate defense regulators (IDRs). These peptides operate through a unique mechanism, influencing the body’s response to injury and infection by promoting an anti-inflammatory, anti-infective, and tissue-healing reaction. Despite lacking direct antibiotic properties, IDRs impact the innate immune system’s responses within the host, enhancing survival rates following infections caused by a broad spectrum of bacterial pathogens, encompassing both Gram-negative and Gram-positive types.

Furthermore, they expedite the healing process after tissue damage induced by various factors, such as bacterial agents, trauma, and the effects of chemotherapy and/or radiation therapy. Extensive preclinical studies have substantiated the efficacy and safety of dusquetide across numerous animal models representing diseases like mucositis, colitis, macrophage activation syndrome (MAS), and bacterial infections. Additionally, promising indications of potential antitumor effects have emerged from multiple in vitro and in vivo xenograft studies.

Dusquetide exhibited favorable safety and tolerability outcomes in a Phase 1 clinical trial involving 84 healthy human volunteers. Subsequent Phase 2 and 3 clinical investigations, involving more than 350 individuals with oral mucositis caused by chemoradiation therapy for head and neck cancer, showcased encouraging efficacy outcomes with SGX942. These results not only indicated positive immediate effects but also hinted at potential long-term supplementary advantages.

Soligenix holds a robust intellectual property stance concerning the IDR technology platform, encompassing the composition of matter rights for dusquetide and its associated analogs. The development of dusquetide stemmed from the breakthroughs and findings by Professors B. Brett Finlay, Ph.D., and Robert Hancock, Ph.D., affiliated with the University of British Columbia, Canada.

“We are very pleased to have SGX945 in Behçet’s Disease granted fast track designation from the FDA,” stated Christopher J. Schaber, PhD, President and Chief Executive Officer of Soligenix. “As demonstrated by the granting of the designation, our previous studies with dusquetide in oral mucositis have clearly validated the biologic activity in aphthous ulcers induced by chemotherapy and radiation. Behçet’s disease is an unmet medical need in which the underlying vasculitis leads to ulceration of the mucous membranes and skin, with up to 18,000 people in the U.S. and as many as one million people worldwide affected by this incurable disease. Given our promising results with aphthous ulcers in oral mucositis, we are hopeful dusquetide will have a role to play in helping underserved patients suffering from this difficult to treat and chronic disease and look forward to initiating the Phase 2 clinical study in 2024.”

Behçet’s Disease is believed to be an autoimmune condition influenced by a combination of genetic predisposition and environmental factors. Its prevalence is notably prominent along the historical “Silk Road” region spanning the Middle East and East Asia, encompassing countries like Turkey, Iran, Japan, and China. In the United States, there are approximately 18,000 documented cases of Behçet’s Disease, while in Europe, the count reaches around 80,000 cases. Globally, it’s estimated that as many as 1,000,000 individuals are living with Behçet’s Disease.

Behçet’s Disease currently lacks a definitive cure, prompting treatments geared toward symptom management. These approaches encompass both ongoing therapies to maintain stability and specific interventions targeting flare-ups, such as mouth, genital, and leg ulcers. Addressing flares often involves immune system suppression using medications like cyclosporine or cyclophosphamide. However, these drugs pose elevated risks of infection, liver and kidney complications, decreased blood cell counts, and high blood pressure. Anti-inflammatory medications, including anti-TNF drugs, are also utilized to manage Behçet’s Disease. Presently, the sole approved medication for this condition is apremilast, primarily employed as a maintenance therapy to prevent oral ulcer formation. Regrettably, apremilast is associated with significant costs and side effects like diarrhea, nausea, upper respiratory tract infections, and headaches.

Pharmaceutical companies play a pivotal role in pioneering and advancing novel therapies for Behçet’s Disease, driving research, innovation, and the development of treatments to alleviate its symptoms and improve patient outcomes. Their efforts are crucial in addressing unmet medical needs and enhancing the quality of life for individuals affected by this condition. The ongoing therapeutics development by pharma and biotech companies including Soligenix, Inc., among others, is set to immensely transform the Behçet’s Disease treatment landscape in the upcoming years. 

Cabaletta Bio Receives Additional FDA Fast Track Designations for CABA-201 in Dermatomyositis and Systemic Sclerosis

On January 8, 2024, Cabaletta Bio, Inc. announced that the U.S. Food and Drug Administration (FDA) has awarded aditional Fast Track Designations to its therpa, CABA-201. This investigational therapy, a fully human CD19-CAR T cell therapy featuring 4-1BB, received the designations for two purposes: enhancing disease activity in patients with Dermatomyositis and addressing associated organ dysfunction in patients with systemic sclerosis (SSc).

CABA-201 is engineered to achieve a deep and temporary reduction in CD19-positive B cells through a single infusion. This approach holds the potential for an “immune system reset,” possibly leading to sustained periods of remission without the need for ongoing therapy in individuals with autoimmune disorders. Cabaletta has already obtained FDA clearance for Investigational New Drug (IND) applications for CABA-201 across various autoimmune conditions, such as systemic lupus erythematosus (SLE), myositis, systemic sclerosis (SSc), and generalized myasthenia gravis (gMG). 

The company is currently conducting four Phase 1/2 clinical trials, encompassing nine cohorts that can progress simultaneously. These trials follow a similar parallel cohort structure, commencing with a starting dose of 1 x 106 cells/kg, and do not require a dose escalation process.

“The additional Fast Track Designations for CABA-201 in both Dermatomyositis and systemic sclerosis, the second and third Fast Track Designations for CABA-201, provide the opportunity for expedited development and review of CABA-201 for the treatment of these autoimmune indications where there is a significant unmet need, despite currently available therapies,” said David J. Chang, M.D., Chief Medical Officer of Cabaletta. “We believe these designations potentially accelerate our ability to launch the first targeted, and potentially curative, cell therapy for autoimmune diseases driven by B cells. We look forward to continuing to leverage our research and translational insights along with our efficient trial designs in order to progress these programs forward for patients in need of better outcomes.”

Dermatomyositi is an autoimmune condition causing severe functional limitations despite standard care. It shows as skin rash, muscle inflammation, affecting around 43,000 in the US, mostly middle-aged women. Treatments include immune suppression or therapies like IVIg, but many patients don’t respond to these interventions, posing ongoing challenges. However, several companies are actively working in the Dermatomyositis therapeutics market to overcome the existing treatment challenges in the market. 

Systemic sclerosis (SSc) is a rare, life-threatening autoimmune condition causing skin and organ fibrosis, posing risks like lung disease and kidney crises. Autoantibodies and B cells’ involvement prompts exploration into CAR T therapy. With around 88,000 affected in the US, treatments are limited to immunosuppressants or specific medications, and although stem cell transplantation offers benefits, its risks restrict widespread use. The scarcity of effective treatments leads to a high mortality risk, with an average survival of about 12 years post-diagnosis. Pharmaceutical companies are pivotal in spearheading the development of innovative therapies for Systemic sclerosis, advancing research and creating new treatment avenues to address this complex condition. The launch of the novel therapies by pharma giants such as Soligenix, and others is poised to revolutionize the Systemic sclerosis treatment landscape, offering hope for improved symptom management, potentially slowing disease progression, and enhancing the quality of life for individuals affected with the condition in the years to come.