PDC

NANJING, China, June 17, 2024 /PRNewswire/ -- At the recent European League Against Rheumatism (EULAR) Congress in Vienna, Austria, Nanjing Leads Biolabs Co., Ltd. (Leads Biolabs) delivered an oral presentation on its highly innovative therapeutic candidate LBL-047. LBL-047 is a first-in-class, long-acting TACI/BDCA2 bispecific antibody fusion protein. LBL-047 is composed of a Transmembrane Activator and a Calcium Modulator and Cyclophilin Ligand Interactor (TACI) domain fused to an antibody targeting Blood Dendritic Cell Antigen 2 (BDCA2). The bispecific antibody is further modified with the YTE mutation on the Fc region to prolong the half-life in circulation, thereby, enabling less frequent dosing, and improved patient compliance. LBL-047 has demonstrated excellent activity and pharmacokinetic properties in multiple preclinical experiments. Significantly inhibit INF-α release Robust depletion of pDCs in vitro and in vivo Superior inhibition of B cell and plasma cell function in vitro and in vivo compared to marketed TACI fusion protein Significantly alleviated clinical symptoms and inhibited B cell and plasma cell function in EAE mouse model (MS model) Excellent PK profile and markedly reduced IgM, IgA, IgG in cynomolgus monkey for up to six weeks These results indicate that LBL-047 can simultaneously inhibit B cell function and deplete interferon-secreting pDCs, thereby attenuating autoimmune activity. This innovative research offers new possibilities for treating a wide range of autoimmune related diseases, including Systemic Lupus Erythematosus (SLE), Cutaneous Lupus Erythematosus (CLE), Lupus Nephritis (LN), Sjogren's Syndrome, and Myasthenia Gravis. Engineered to significantly prolong the dosing interval, LBL-047 presents an optimal product profile for subsequent clinical and commercial development. Huang Xiao, Vice President of Discovery Research at Leads Biolabs, said: "EULAR is a highly anticipated event in the fields of rheumatology and immunology. We are honored to be featured in this prestigious gathering of over 18,000 experts and scholars from more than 130 countries to share the exciting data we have generated. LBL-047, independently developed and fully owned by Leads Biolabs, represents a significant achievement arising from our differentiated innovation strategy. Its unique design is based on our profound understanding of autoimmune diseases and target mechanisms, integrating extensive antibody engineering technologies and optimization efforts. We are very pleased with the results we have seen in preclinical studies. Leads Biolabs is dedicated to our corporate philosophy of 'care for life, focus on innovation, and win-win cooperation,' and is committed to providing safer and more effective treatment options for patients. Currently, LBL-047 is in the preclinical research stage, and we will continue to efficiently promote the development of this drug candidate to bring effective treatments to patients with autoimmune diseases as soon as possible." About LBL-047 B cells and pDCs play a crucial and synergistic role in the pathogenesis of many autoimmune diseases. Inhibiting the function of B cells and pDCs is a potential therapeutic strategy for treating various autoimmune diseases. LBL-047 is a long-acting TACI/anti- BDCA2 bispecific fusion protein, obtained by fusing an engineered TACI domain with a defucosylated anti-BDCA2 humanized monoclonal antibody. TACI is the natural high-affinity receptor for B cell activation factor of the tumor necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL), which are key cytokines that promote B cell and plasma cell survival, maturation, and function. Engineered TACI domain can be used to trap BAFF and APRIL, inhibiting B-cell function. BDCA2 is specifically expressed on pDCs and BDCA2 agonist antibody can suppress the IFNs release. Additionally, anti-BDCA2 antibodies can directly eliminate pDCs through mechanisms such as ADCC, inhibiting pDC-mediated immune responses. The defucosylated anti-BDCA2 antibody has stronger ADCC activity, and the introduction of YTE mutation in the Fc region further prolongs the half-life of the antibody. Preclinical studies have demonstrated that LBL-047 can potently inhibit the functions of B cells and pDCs simultaneously, and possesses excellent pharmacokinetic properties, indicating broad clinical applications and market prospects in the treatment of various autoimmune diseases. About Leads Biolabs Nanjing Leads Biolabs Co., Ltd. is a clinical-stage biotechnology company founded in Nanjing by a team of senior U.S.-trained antibody drug developers. Since 2014, Leads Biolabs has been dedicated to the discovery and development of novel antibody drugs with independent intellectual property rights for the treatment of oncology and other major diseases of high unmet medical needs, particularly the challenges in cancer immunotherapy. Our extensive R&D pipeline consist of more than twenty novel tumor immunotherapy, autoimmunity and ADC molecules based on monoclonal and bispecific antibody technology platforms. Leads Biolabs is committed to providing safe, effective, accessible, and affordable new drugs to address the unmet needs of patients around the world.

Novel camptothecin-peptide conjugates are well tolerated and associated with significant tumor regression in colorectal cancer and triple-negative breast cancer xenograft models SORT1 gene silencing results in drastic decrease in peptide-drug conjugate uptake which supports a SORT1-mediated internalization process Poster presentation broadens evidence supporting potential utility of platform-derived peptide-drug conjugates alone or in combination in numerous SORT1-positive tumors MONTREAL, April 08, 2024 (GLOBE NEWSWIRE) -- Theratechnologies Inc. (“Theratechnologies” or the “Company”) (TSX: TH) (NASDAQ: THTX), a biopharmaceutical company focused on the development and commercialization of innovative therapies, today presented preclinical data that highlight the versatility and flexibility of the Company’s SORT1+ Technology™ platform. In a poster session at the 2024 annual meeting of the American Association for Cancer Research (AACR) in San Diego, Calif., researchers reported that Theratechnologies’ investigational camptothecin-peptide conjugates are well tolerated and associated with significant tumor regression in colorectal cancer (CRC) and triple-negative breast cancer (TNBC) xenograft models. The study also demonstrated synergistic anti-tumor efficacy and good tolerability with the combination of two peptide drug conjugates with different payloads. “The preclinical data presented at AACR add to the sizeable body of evidence supporting the potential utility of the SORT1+ Technology™ platform as an engine for the development of novel peptide-drug conjugates to treat various types of cancer,” said Christian Marsolais Ph.D., Senior Vice President and Chief Medical Officer at Theratechnologies. “In addition to our lead peptide-drug conjugate, sudocetaxel zendusortide, these latest data highlight the promising tolerability and anti-tumor effects of our investigational camptothecin-peptide conjugates, further demonstrating the versatility and flexibility of the platform. We welcome discussions with potential partners who are interested in the further development of these innovative therapies.” The SORT1+ Technology™ platform relies on the use of a novel, proprietary peptide called TH19P01, which can be conjugated (attached) to numerous well-characterized anticancer drugs. Theratechnologies designed TH19P01 to interact with and be transported by the scavenger receptor sortilin (SORT1), which is involved in protein internalization, sorting, and trafficking, and is expressed in multiple tumor types. Targeting SORT1 with platform-derived peptide-drug conjugates (PDCs) leads to receptor-mediated internalization (endocytosis) of anticancer agents. Once inside cancer cells, active drug is released from the peptide and exerts its cytotoxic effect directly on the cancer cell. In the poster presented at AACR, the investigators noted that SORT1 gene silencing inhibits camptothecin-conjugate uptake in human HT-29 colorectal adenocarcinoma cells. This observation suggests that these PDCs enter cancer cells via a SORT1-mediated internalization process. The investigators also described the preclinical effects of three PDCs – TH2101, TH2205, and TH2310 – that have a cytotoxic payload of SN-38, the active metabolite of irinotecan, an anticancer agent that is derived from the Chinese tree Camptotheca acuminate. In addition, the poster summarized the activity of another PDC, TH2303, which carries an exatecan payload, a structural analog of camptothecin. Compared to unconjugated irinotecan, the exatecan- and SN-38-conjugates exerted greater anti-proliferative activities against CRC cells in mice. In two different CRC xenograft models, as well as in the TNBC xenograft model, TH2303 was associated with increased tumor growth inhibition and greater tolerability compared to unconjugated exatecan or irinotecan. In another experiment described in the poster, the combination of two SORT1-targeting PDCs – sudocetaxel zendusortide (TH1902) and TH2101, which have a synergistic anti-tumor effect at reduced doses, led to increased tumor growth inhibition and some complete responses in the HT-29 xenograft model, compared to either PDC administered alone. The combination also was well tolerated. “The significant tumor regression following combination therapy is notable because the HT-29 xenograft model is known for its resistance to multiple cytotoxic drugs,” commented Prof. Borhane Annabi, Chair in Cancer Prevention and Treatment in the Chemistry Department at the Université du Québec à Montréal. “That observation, along with the impressive anticancer efficacy of the camptothecin-peptide conjugates when administered alone, underscores the potential feasibility of this approach in treating various tumor types.” A copy of the AACR poster, as well as a second poster presented at the conference, which reinforces existing data for the Company’s lead investigational PDC sudocetaxel zendusortide (TH1902) in activating anti-PD-L1 immunotherapy tumor cell-killing in SORT+1 cancers, can be found at the Theratechnologies website. About Sudocetaxel Zendusortide (TH1902) and SORT1+ Technology™ Sudocetaxel zendusortide is a first-of-its-kind sortilin receptor (SORT1)-targeting PDC, and the first compound to emerge from the Company’s broader licensed oncology platform. A new chemical entity, sudocetaxel zendusortide employs a cleavable linker to conjugate (attach) a proprietary peptide to docetaxel, a well-established cytotoxic chemotherapeutic agent used to treat many cancers. The FDA granted Fast Track designation to sudocetaxel zendusortide as a single agent for the treatment of all sortilin-positive recurrent advanced solid tumors that are refractory to standard therapy. Sudocetaxel zendusortide is currently being evaluated in a Phase 1 clinical trial. Theratechnologies has established the SORT1+ TechnologyTM platform as an engine for the development of PDCs that target SORT1, which is expressed in multiple tumor types. SORT1 is a “scavenger” receptor that plays a significant role in protein internalization, sorting, and trafficking. Expression of SORT1 is associated with aggressive disease, poor prognosis, and decreased survival. It is estimated that SORT1 is expressed in 40% to 90% of endometrial, ovarian, colorectal, triple-negative breast (TNBC), and pancreatic cancers, making this receptor an attractive target for anticancer drug development. About Theratechnologies Theratechnologies (TSX: TH) (NASDAQ: THTX) is a biopharmaceutical company focused on the development and commercialization of innovative therapies addressing unmet medical needs. Further information about Theratechnologies is available on the Company's website at , on SEDAR+ at and on EDGAR at . Follow Theratechnologies on Linkedin and X (formerly Twitter). Forward-Looking Information This press release contains forward-looking statements and forward-looking information (collectively, the “Forward-Looking Statements”) within the meaning of applicable securities laws, that are based on management’s beliefs and assumptions and on information currently available to it. You can identify forward-looking statements by terms such as “may”, “will”, “should”, “could”, “promising”, “would”, “outlook”, “believe”, “plan”, “envisage”, “anticipate”, “expect” and “estimate”, or the negatives of these terms, or variations of them. The Forward-Looking Statements contained in this press release include, but are not limited to, statements regarding the development of multiple PDCs, including, without limitation, camptothecin-peptide conjugates and sudocetaxel zendusortide, their use and the potential benefits to be derived from their use. Although the Forward-Looking Statements contained in this press release are based upon what the Company believes are reasonable assumptions in light of the information currently available, investors are cautioned against placing undue reliance on these statements since actual results may vary from the Forward-Looking Statements contained in this press release. These assumptions include, without limitation, that the Company’s Phase 1 clinical trial using sudocetaxel zendusortide will be successful, that signs of efficacy will be observed in such Phase 1 clinical trial and no untoward side effects will be reported, and that the findings observed from the preclinical work conducted on new PDCs will be replicated into human subjects. Forward-Looking Statements assumptions are subject to a number of risks and uncertainties, many of which are beyond the Company’s control, that could cause actual results to differ materially from those that are disclosed in or implied by such Forward-Looking Statements. These risks and uncertainties include, but are not limited to, the lack of observation of strong efficacy results from the Phase 1 clinical trial using sudocetaxel zendusortide, the reporting of adverse side effects from the use of sudocetaxel zendusortide leading to a halt of the clinical trial, and that the findings observed from preclinical work conducted on new PDCs are not observed when those are administered into human subjects. We refer current and potential investors to the “Risk Factors” section (Item 3.D) of our Form 20-F dated February 21, 2024, available on SEDAR+ at and on EDGAR at under Theratechnologies’ public filings. The reader is cautioned to consider these and other risks and uncertainties carefully and not to put undue reliance on forward-looking statements. Forward-Looking Statements reflect current expectations regarding future events and speak only as of the date of this press release and represent our expectations as of that date. We undertake no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise, except as may be required by applicable law. Contacts: Investor inquiries: Philippe Dubuc Senior Vice President and Chief Financial Officer pdubuc@theratech.com 1-438-315-6608 Media inquiries: Julie Schneiderman Senior Director, Communications & Corporate Affairs communications@theratech.com 1-514-336-7800

– PRTX007 program to support DTRA’s efforts to establish biological defense solution against Lassa fever and other hemorrhagic viruses – SAN DIEGO--(BUSINESS WIRE)-- Primmune Therapeutics, a biotech company harnessing the power of the innate immune system, today announced that it was awarded a $22,480,552 contract by the United States Defense Threat Reduction Agency (DTRA) to develop PRTX007 as an oral broad spectrum antiviral TLR7 agonist for the treatment of Lassa fever. PRTX007 is a clinical-stage novel oral small molecule that specifically activates toll-like receptor 7 (TLR7), which drives the innate immune system’s primary response to viral infections, enabling broad spectrum antiviral activity. The objective of the program is to evaluate the efficacy of PRTX007 in a series of animal models for Lassa fever and establish an effective treatment method of Lassa virus in humans. In addition, the program will support the development of US-based manufacturing capabilities. “The scientific community has long recognized the therapeutic potential of systemically acting toll-like receptor agonists in the treatment of acute and chronic viral diseases, precancerous lesions and solid tumors,” said James Appleman, Ph.D., Co-founder and Chief Scientific Officer at Primmune Therapeutics. “PRTX007 is unique in that administration engages a coordinated innate and adaptive immune response which is required for therapeutic benefit, while avoiding excessive systemic inflammation – historically, a challenge associated with TLR7 agonists.” Primmune’s PRTX007 program will support DTRA’s efforts to counter current threats and challenges from Lassa fever and other hemorrhagic viruses through the development of a timely and effective biological defense solution. Primmune and DTRA expect the program to be completed by June 30, 2026. “Primmune has demonstrated broad spectrum antiviral activity with PRTX007 and with related compounds from our discovery and development program,” said Charlie McDermott, President, Chief Executive Officer and Director of Primmune Therapeutics. “PRTX007 has been shown to be amenable to scale-up, long-term storage and tableting, with the potential to be deployed as a single agent or in combination with direct antiviral compounds or other therapeutic modalities – underscoring its potential utility as a first line of defense against future novel pathogens in real-world settings.” Research and development funds in the amount of $845,610.00 were initially provided to Primmune on January 30, 2024. The contract agreement includes committed funding of $10.6 million, which will be provided to Primmune across a 14-month base period, with the potential to receive option period funding in the amount of $11.9 million, pending the achievement of performance milestones throughout the base period. “Treating African hemorrhagic fever viruses such as Lassa fever, Marburg virus disease and Ebola virus disease poses many challenges due to the underlying pathophysiology of the diseases and their highly infectious nature,” said Curtis Scribner, M.D., Chief Medical Officer at Primmune Therapeutics. “PRTX007’s novel immunologic approach has the potential for combination use with direct acting anti-viral agents – enabling widely applicable utility in the treatment of Lassa fever and other hemorrhagic viruses.” About PRTX007 PRTX007 is Primmune’s lead clinical development candidate. In a 130 person healthy volunteer SAD/MAD clinical study, PRTX007 was well-tolerated while also driving controlled, long-term systemic stimulation of the innate immune response. PRTX007 administration uniquely activates selected plasmacytoid dendritic cells (pDCs) functions, leading to a systemic immune poly-IFN response without stimulating production of NF-κB-driven proinflammatory factors like IL-6, TNFα or IL-1β. These activated pDCs directly deliver interferons to target cells by paracrine transfer. Conceptually, this is equivalent to administering a therapeutically effective cocktail of all Type I/III IFNs while avoiding the associated side effects and adverse events. Furthermore, repeated PRTX007 administration leads to pDC-mediated systemic activation of CD8+ T cells and NK cells, both of which are important for treatment of viral diseases and cancer. About Primmune Therapeutics Primmune Therapeutics is a clinical-stage biotech harnessing the power of the innate immune system for therapeutic benefit through development of novel small molecule, orally administered toll-like receptor 7 (TLR7) agonists. For more information, please visit .