CD86

PITTSBURGH, May 15, 2024 (GLOBE NEWSWIRE) -- Krystal Biotech, Inc. (the “Company”) (NASDAQ: KRYS), a commercial-stage biotechnology company, announced today that the Company will be presenting new preclinical data on respiratory genetic medicine candidates KB407 and KB408 at the American Thoracic Society (ATS) 2024 International Conference being held from May 17-22, 2024 in San Diego, California. KB407 and KB408 are modified, replication-defective, non-integrating HSV-1 vectors formulated for inhaled delivery to the lung via nebulization. KB407 encodes two full-length copies of cystic fibrosis transmembrane conductance regulator (CFTR) and is under investigation for the treatment of cystic fibrosis irrespective of underlying patient mutation. KB408 encodes two full-length copies of alpha-1 antitrypsin and is under investigation for the treatment of alpha-1 antitrypsin deficiency (AATD). Both KB407 and KB408 are being evaluated in ongoing Phase 1 studies. Data presented at ATS will include new preclinical data related to KB407 transduction of fully differentiated, patient airway epithelial cell-derived apical out airway organoids and production of full-length and fully glycosylated CFTR, as well as an overview of KB408 IND-enabling studies conducted to support initiation of the ongoing Phase 1 SERPENTINE-1 study in patients with AATD. Poster presentation details are as follows: Title: Murine Toxicology Study of Repeat-Dose Inhaled KB408, an HSV-1-Based Vector for the Treatment of Alpha-1 Antitrypsin Deficiency Presenter: Sara Artusi, PhDDate and Time: May 20, 2024 from 11:30AM to 1:15PM PTPoster Session: B70: COPD in the Spotlight: Insights into Disease Pathogenesis Poster Number: P659 Title: Evaluation of KB407, an HSV-1-Based Gene Therapy Vector for the Treatment of Cystic Fibrosis, in Healthy and Patient-Derived Airway Cells Including an Apical-out Diseased Airway Organoid ModelPresenter: Sara Artusi, PhDDate and Time: May 21, 2024 from 11:30AM to 1:15PM PTPoster Session: C70: From Buds to Breath: Mechanisms and Pathogenesis of Lung Development Poster Number: P122 The posters will be available to conference attendees. Following the presentation, the posters will also be available to view online on the Investor section of the Company’s website. About Krystal Biotech, Inc.Krystal Biotech, Inc. (NASDAQ: KRYS) is a commercial-stage biotechnology company focused on the discovery, development and commercialization of genetic medicines to treat diseases with high unmet medical needs. VYJUVEK® is the Company’s first commercial product, the first-ever redosable gene therapy, and the first medicine approved by the FDA for the treatment of dystrophic epidermolysis bullosa. The Company is rapidly advancing a robust preclinical and clinical pipeline of investigational genetic medicines in respiratory, oncology, dermatology, ophthalmology, and aesthetics. Krystal Biotech is headquartered in Pittsburgh, Pennsylvania. For more information, please visit http://www.krystalbio.com, and follow @KrystalBiotech on LinkedIn and X (formerly Twitter). CONTACTInvestors and Media:Stéphane Paquette, PhDKrystal Biotechspaquette@krystalbio.com

Capital infusion will support botensilimab and balstilimab (BOT/BAL) clinical development, confirmatory Phase 3 trial, and launch readiness activities Ligand entitled to royalties and milestone payments on six Agenus-partnered programs as well as royalties on future global net sales generated by BOT/BAL Transaction allows for a syndication of up to an additional $125 million in capital JUPITER, Fla. and LEXINGTON, Mass.--(BUSINESS WIRE)-- Ligand Pharmaceuticals Incorporated (Nasdaq: LGND) and Agenus Inc. (Nasdaq: AGEN), a leader in discovering and developing novel immunological agents to treat various cancers, today announced that the companies have entered into a royalty financing agreement to support Agenus’ key development initiatives in the ongoing BOT/BAL clinical development program, including its planned confirmatory Phase 3 trial in its lead indication of patients with metastatic, relapsed/refractory colorectal cancer not microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR), who are without active liver metastases (r/r MSS CRC NLM), along with other launch readiness activities. Under the terms of the agreement, Ligand will pay $75 million to Agenus at closing. In addition, Ligand has the option to invest an additional $25 million on the same terms on a pro rata basis. In return for the initial $75 million payment, Ligand will receive 18.75% of the future royalties and 31.875% of the future milestone payments related to six of Agenus’ clinical-stage partnered oncology programs, including BMS-986442 (Bristol Myers Squibb), AGEN2373 (Gilead Sciences), INCAGN2385 and INCAGN2390 (Incyte), MK-4830 (Merck), and UGN-301 (UroGen Pharma). Ligand’s portion of the milestones related to these six programs has the potential to exceed $400 million, with royalties in the low single digits. In addition, Ligand will also receive a 2.625% royalty on future global net sales generated by BOT/BAL. The royalties and milestone payments owed to Ligand could be adjusted up or down based upon pre-determined future events and achievements of certain milestones. “This partnership with Agenus gives us an interest in multiple oncology products diversified across targets and indications, including royalties on BOT/BAL and several partnered oncology programs being developed by experienced biopharmaceutical companies,” commented Todd Davis, CEO of Ligand. “We are encouraged by Agenus’ progress to move BOT/BAL forward in the metastatic, relapsed/refractory colorectal cancer setting, in addition to other major indications, including pancreatic cancer, lung cancer, and melanoma. This demonstrates the potential value BOT/BAL could deliver to patients, as well as the significant revenue potential of this broad and highly differentiated program. Our seasoned investment team spent significant time and effort conducting diligence on each of these unique and valuable assets.” As part of the agreement, the companies have also agreed to allow Agenus to syndicate up to an additional $125 million, potentially bringing the total capital infusion up to $200 million. This strategic collaboration will further validate BOT/BAL’s potential as a transformative treatment for patients with solid tumor malignancies and enhances Agenus’ ability to advance this promising therapy. Garo Armen, Chairman and Chief Executive Officer of Agenus, commented, “We are pleased to partner with Ligand, a company that recognizes the paradigm-shifting potential of BOT/BAL in delivering benefit to patients across the solid tumor landscape. Ligand also recognizes the potential impact of our ongoing partnered programs, many of which are showing promise in the clinic. This collaboration enables both parties to benefit in the future potential success of these assets while simultaneously enabling Agenus to accelerate our efforts to bring BOT/BAL to patients in need.” Over 900 patients have been treated with BOT/BAL in clinical trials across nine different difficult to treat solid tumor cancers. The novel therapeutic regimen has demonstrated the potential to be combined with chemotherapy and other standard of care therapies, and as an immunotherapy-only combo in CRC, one of the most prevalent solid tumors globally. In April 2023, Agenus was granted Fast Track Designation from the U.S. Food and Drug Administration (FDA) for the investigation of the BOT/BAL combination in patients with r/r MSS CRC NLM. Patients targeted with this designation are heavily pretreated with standard of care chemotherapy, anti-VEGF and anti-EGFR if RAS wild type. About Agenus Agenus is a leading immuno-oncology company targeting cancer and infectious diseases with a comprehensive pipeline of immunological agents. The company’s mission is to expand patient populations benefiting from cancer immunotherapy through combination approaches, using a broad repertoire of antibody therapeutics, adoptive cell therapies (through MiNK Therapeutics) and adjuvants (through SaponiQx). Agenus is headquartered in Lexington, MA. For more information, visit or @agenus_bio. Information that may be important to investors will be routinely posted on Agenus’ website and social media channels. About Botensilimab Botensilimab is an investigational multifunctional anti-CTLA-4 immune activator (antibody) designed to boost both innate and adaptive anti-tumor immune responses. Its novel design leverages mechanisms of action to extend immunotherapy benefits to "cold" tumors which generally respond poorly to standard of care or are refractory to conventional PD-1/CTLA-4 therapies and investigational therapies. Botensilimab augments immune responses across a wide range of tumor types by priming and activating T cells, downregulating intratumoral regulatory T cells, activating myeloid cells and inducing long-term memory responses. Over 900 patients have been treated with botensilimab in phase 1 and phase 2 clinical trials. Botensilimab alone, or in combination with Agenus’ investigational PD-1 antibody, balstilimab, has shown clinical responses across nine metastatic, late-line cancers. For more information about botensilimab trials, visit with the identifiers NCT03860272, NCT05608044, NCT05630183, and NCT05529316. About Agenus Partnered Programs BMS 986-442 is a novel first-in-class anti-TIGIT and CD96 bispecific antibody engineered with an enhanced Fc region for high binding affinity and improved T and NK cell activation. MK-4830 is a potentially first-in-class human IgG4 monoclonal antibody targeting the immunoglobulin-like transcript 4 (ILT4) receptor. AGEN2373 is a fully human monoclonal antibody designed to boost the immune response to cancer cells by enhancing CD137 co-stimulatory signaling in activated immune cells. The unique binding properties of AGEN2373 are expected to limit its activity outside of the tumor site and mitigate toxicities that may be associated with systemic activation of CD137 in humans.UGN-301 (zalifrelimab) is a novel, fully human monoclonal immunoglobulin G1 (IgG1) designed to block CTLA-4 (cytotoxic T-lymphocyte associated antigen 4) from interacting with its ligands CD80 and CD86. CTLA-4 is a negative regulator of immune activation that is considered a foundational target within the immuno-oncology market. UroGen has a license to use zalifrelimab via intravesical delivery for treatment of cancers of the urinary tract. INCAGN2385, a novel human Fc silent IgG1 monoclonal antibody targeting LAG-3, blocking binding to MHC II. INCAGN3920, a novel recombinant human IgG1 monoclonal antibody targeting TIM-3. About Ligand Pharmaceuticals Ligand is a biopharmaceutical company enabling scientific advancement through supporting the clinical development of high-value medicines. Ligand does this by providing financing, licensing our technologies or both. Its business model seeks to generate value for stockholders by creating a diversified portfolio of biopharmaceutical product revenue streams that are supported by an efficient and low corporate cost structure. Ligand’s goal is to offer investors an opportunity to participate in the promise of the biotech industry in a profitable and diversified manner. Its business model focuses on funding programs in mid- to late-stage drug development in return for economic rights, purchasing royalty rights in development stage or commercial biopharmaceutical products and licensing its technology to help partners discover and develop medicines. Ligand partners with other pharmaceutical companies to leverage what they do best (late-stage development, regulatory management and commercialization) in order to generate its revenue. Ligand’s Captisol® platform technology is a chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs. Ligand has established multiple alliances, licenses and other business relationships with the world’s leading biopharmaceutical companies including Amgen, Merck, Pfizer, Jazz, Takeda, Gilead Sciences and Baxter International. For more information, please visit Follow Ligand on X @Ligand_LGND. We use our investor relations website and X as a means of disclosing material non-public information and for complying with our disclosure obligations under Regulation FD. Investors should monitor our website and our X account, in addition to following our press releases, SEC filings, public conference calls and webcasts. Forward-Looking Statements This news release contains forward-looking statements by Ligand that involve risks and uncertainties and reflect Ligand's judgment as of the date of this release. Words such as “plans,” “believes,” “expects,” “anticipates,” and “will,” and similar expressions, are intended to identify forward-looking statements. These forward-looking statements include, without limitation, statements regarding: Ligand’s future royalty payments due under its agreement with Agenus, the potential impact of six Agenus-partnered programs with some of the leading biopharma companies in the world, including BMS-986442 (Bristol Myers Squibb), AGEN2373 (Gilead Sciences), INCAGN2385 and INCAGN2390 (Incyte), MK-4830 (Merck), and UGN-301 (UroGen Pharma), the trial and regulatory success of Agenus’ upcoming Phase 3 trial of botensilimab in combination with balstilimab (“BOT/BAL”) for patients with metastatic, refractory colorectal cancer that is not MSI-H/dMMR and who do not have liver metastases, the potential high patient impact, and revenue potential, of BOT/BAL program, the paradigm-shifting potential of BOT/BAL program in delivering benefits to patients across the metastatic solid tumor landscape and in generating significant revenues, Ligand may not receive expected revenue under this agreement or others, Ligand or its partners may not be able to protect their intellectual property, and patents covering certain products and technologies may be challenged or invalidated which could expose Ligand to significant liabilities and have a material adverse effect on the company. The failure to meet expectations with respect to any of the foregoing matters may reduce Ligand's stock price. Additional information concerning these and other risk factors affecting Ligand can be found in prior press releases available at as well as in Ligand's public periodic filings with the Securities and Exchange Commission available at . Ligand disclaims any intent or obligation to update these forward-looking statements beyond the date of this release, including the possibility of additional license fees and milestone revenues we may receive. This caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. This press release contains forward-looking statements that are made pursuant to the safe harbor provisions of the federal securities laws, including statements relating regarding partnered programs, including BMS-986442, AGEN2373, INCAGN2385, INCAGN2390, MK-4830, and UGN-301 and to the use of botensilimab and balstilimab, for instance, statements regarding therapeutic benefit and efficacy, mechanism of action (including validation of mechanism of action), potency, durability, and safety profile (including the absence of specific toxicities) of the Company’s therapeutic candidates; and any other statements containing the words "may," "believes," "expects," "anticipates," "hopes," "intends," "plans," "forecasts," "estimates," "will," “establish,” “potential,” “superiority,” “best in class,” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially. These risks and uncertainties include, among others, the factors described under the Risk Factors section of our most recent Quarterly Report on Form 10-Q or Annual Report on Form 10-K filed with the Securities and Exchange Commission. Agenus cautions investors not to place considerable reliance on the forward-looking statements contained in this release. These statements speak only as of the date of this press release, and Agenus undertakes no obligation to update or revise the statements, other than to the extent required by law. All forward-looking statements are expressly qualified in their entirety by this cautionary statement. View source version on businesswire.com: Contacts For Ligand: Investors: Michael Jeong investors@ligand.com (561) 214-4232 LifeSci Advisors Bob Yedid bob@lifesciadvisors.com (516) 428-8577 Media: Kellie Walsh media@ligand.com (914) 315-6072 For Agenus: Investors: (917) 362-1370 investor@agenusbio.com Media: (612) 839-6748 communications@agenusbio.com Source: Ligand Pharmaceuticals Incorporated View this news release online at:

Researchers have developed a method to determine how reliably target proteins can be labeled using super-resolution fluorescence microscopy. LMU researchers have developed a method to determine how reliably target proteins can be labeled using super-resolution fluorescence microscopy. Modern microscopy techniques make it possible to examine the inner workings of cells in astonishing detail. "We can now observe the arrangement and interaction of individual proteins under the microscope," says Professor Ralf Jungmann, Chair of Molecular Physics of Life at LMU and Max Planck Fellow at the MPI of Biochemistry. The biophysicist's team recently developed the revolutionary RESI (Resolution Enhancement by Sequential Imaging) method. This technique can be used to improve the resolution of fluorescence microscopy down to the Ångström scale -- far below the classical diffraction limit of light. DNA-conjugated marker molecules, which the researchers attach precisely to the molecules they want to understand better, are crucial for this. Jungmann's team has now presented a technique in the journal Nature Methods that can be used to quantify how well biomarker molecules bind to the target proteins. "This is absolutely crucial if you want to make quantitatively reliable statements," explains the physicist. If you know the labeling efficiency, you can carry out spatially resolved proteomics in this way. This allows you to find out not only what individual proteins do in a cell, but also to what extent they are present and how their quantity and behavior change under certain circumstances. "But this is only possible if we can assess how well the labeling has worked." This is because only labeled proteins emit flashes of light under the microscope and thus become visible. Reliable and versatile The method developed by Jungmann's team makes this assessment possible by adding a reference biomarker to the target proteins. This marker "glows" in a different color during microscopy, so that successfully marked proteins appear in two colors. Jungmann's team demonstrated this using the membrane protein CD86, among others: The reference produces a pink fluorescence, the actual marker a bluish one. This creates a pattern of innumerable pink and blue points of light. Where the marking did not work, only the reference lights up individually. The marking efficiency is calculated from the ratio of double and single illuminated molecules. The method offers several advantages compared to previous methods for determining binding efficiency: "It works not only in vitro, but also in vivo, i.e. in the context of intact cells," explains Jungmann. "The technique can also be applied to a variety of different target molecules, biomarkers, and samples and is compatible with a whole range of super-resolution methods." A reliable and widely applicable means of assessing marker efficiency is crucial to ensure accurate data evaluation and enable reliable comparisons between different binders, labeling conditions, and research laboratories. The authors of the study are certain that the new quantification method has paved the way for significantly expanding the potential of their super-resolution microscope method: "Now we can also consider specific biomedical applications in which the quantitative detection of proteins and processes is of great importance," says Jungmann. This includes cancer research, for example, where information about interactions between proteins on the cell surface and drugs with molecular resolution is essential for the development of new types of medication.