CD9

Kling reports on advancing pipeline of therapeutic antibodies targeting novel antigens discovered with its best-in-class B-cell screening platform, Kling-Select Progress on in vitro and in vivo validation of two highly specific tumor antigens is reported: CD43s, a sialylated-glyco epitope, and U5snRNP200, an ectopically expressed antigen highly specific for AML blast Lead program KBA1412 is advancing in a Phase 1 clinical study, targeting advanced solid malignant tumors AMSTERDAM, Feb. 22, 2024 /PRNewswire/ -- Kling Biotherapeutics ("Kling" or "the Company"), a clinical stage biotech company developing antibody-based drugs against targets identified from its primary B-cell screening platform, today announces that it will be presenting findings demonstrating the power of its clinically validated, best-in-class, B cell screening platforms, Kling-Select and Kling-Evolve, at the ESMO Targeted Anticancer Therapies Congress, in Paris, France on 26 February. Michael Koslowski, Chief Executive Officer at Kling Bio, said: "Our findings consistently highlight and validate our world class, proprietary primary B cell screening platform and its ability to efficiently identify novel therapeutic targets and antibodies. Our aim is to maximise disease fighting antibodies and find a cure for all patients battling illnesses which include cancer and infectious diseases. Our lead clinical candidate KBA1412, a unique and previously undiscovered epitope of CD9, is advancing in a Phase 1 study, demonstrating a clean and safe profile in patients with advanced solid tumors. We look forward to sharing data in the foreseeable future and exploring the therapeutic potential of snRNP200 and our uniquely identified CD43 glycoform." Poster one, entitled " KBA1413, an antibody derived from a cured AML patient, recognizes a unique CD43 glycoform shared by AML, MDS and solid cancer cells," details the identification of KBA1413, a fully human antibody screened from a single acute myeloid leukemia (AML) patient who remains in long term remission following allogeneic hematopoietic stem cell transplantation. The antibody identified using Kling's proprietary B cell screening platform, Kling-Select, recognised a unique, previously undescribed, sialylated epitope on CD43 that is reactive to freshly isolated blasts of over 60 randomly selected AML and myelodysplastic syndrome (MDS) patients. It also recognised CD43 on several solid tumor indications, including melanoma and breast cancer. KBA1413 triggered TR NK-mediated antibody dependent cell-mediated cytotoxicity (ADCC) against AML cells both in vitro and in vivo, suggesting that the antibody played a role in the graft versus leukemia response of the original donor patient. KBA1413 was made into a bispecific T-cell engaging antibody (bTCE), to increase its therapeutic potential and induced potent cytotoxicity in vitro and in vivo on cell lines in primary AML. Data demonstrates that KBA1413 warrants further development as a potent and promising treatment candidate for AML, MDS and solid tumors. Poster two, entitled " snRNP200 reactive antibodies isolated from multiple AML patients show promise for targeted therapy," details how Kling's proprietary Kling-Select platform has the ability to identify new therapeutic target-antibody pairs to improve patient outcomes by interrogating the B cell repertoire of patients that have achieved remission via a strong tumor-directed immune response. The Kling-Select platform was used to discover and characterise anti-snRNP200 antibodies from three AML patients that have achieved complete response after allogeneic stem cell transplantation, establishing that anti-snRNP200 specifically and selectively bind to AML cell lines that display snRNP200 on the outer cell surface. These findings have been independently confirmed[2] and show that snRNP200 surface expression is limited to malignant cells and not expressed on normal hematopoietic stem cell progenitors. Kling will further explore the therapeutic potential of anti-snRNP200 with affinity matured variants produced with Kling-Evolve. A first-in-human, Phase 1 clinical trial on Kling's first-in-class anti-CD9 antibody in patients with advanced solid malignant tumors is ongoing and can be found on under the identifier NCT05501821. All accepted abstracts will be published online only in the ESMO TAT 2024 Abstract Book, a supplement to the ESMO journal, ESMO open. Details of the conference and poster presentations are as follow: Poster Title: KBA1413, an antibody derived from a cured AML patient, recognizes a unique CD43 glycoform shared by AML, MDS and solid cancer cells Authors: V. Clerico Mosina, M. Kedde, B. Pieters, B. Monica, K. Maijoor, R. Schotte, A. Bakker, M. Koslowski, S. Gullà[1] Date and Time: 26 February, 17:15-18:15 CET Session: Cocktail and Poster Display Session Location: Hall Bordeaux Presentation Number: 11P Poster Title: snRNP200 reactive antibodies isolated from multiple AML patients show promise for targeted therapy Authors: S. Baumann, M. Kedde, B. Monica, K. Maijoor, R. Schotte, A. Bakker, J. M. Koslowski, S. Gullà[1] Date and Time: 26 February, 17:15-18:15 CET Session: Cocktail and Poster Display Session Location: Hall Bordeaux Presentation Number: 11P 1. Kling Biotherapeutics, Amsterdam, Netherlands 2. National Library of Medicine. About Kling Biotherapeutics Kling Biotherapeutics is a clinical-stage, privately held biotech company focused on discovery and development of antibody based therapeutics. The company is headquartered in Amsterdam, Netherlands with a fully owned IP portfolio that covers platform technologies Kling-Select and Kling-Evolve for the simultaneous discovery of novel targets and identification of fully human antibodies directly from patient-derived B cells. Kling-Select relies on a fully-owned and clinically-validated B cell immortalization and screening technology to identify novel therapeutic targets and antibody binders from patients with exceptional clinical responses. This technology has successfully identified novel neutralising antibodies for various infectious diseases such as RSV (nirsevimab/Beyfortus), Covid, and Influenza. More recently, Kling-Select has been applied to peripheral and tumor-infiltrating B cells derived from cancer patients and produced a portfolio of novel and selective target-antibody pairs. The unbiased nature of this discovery platform allows identification of novel targets and unique epitopes inaccessible to traditional target discovery approaches. Kling-Evolve enables the ex vivo affinity maturation of B cell clones against targets of interest. This powerful technology can be used for the rapid evolution of neutralizing antibodies against emerging viral variants or for affinity and selectivity improvement of oncology assets. Kling Biotherapeutics is progressing a unique pipeline of oncology programs with KBA1412, a first-in-class CD9 antibody, being tested in a Phase 1 clinical trial. Details of the trial can be found on clinicaltrials.gov under identifier NCT05501821. About ESMO ESMO's core mission is to improve the quality of cancer care, from prevention and diagnosis all the way to palliative care and patient follow-up. It is to educate – doctors, cancer patients and the general public – on the best practices and latest advances in oncology. And it is to promote equal access to optimal cancer care for all patients. SOURCE Kling Biotherapeutics

Malignant melanoma is a relatively aggressive type of skin cancer. When detected early, it is usually treatable by surgical resection only, but metastases develop often spreading to distant areas. Currently, tumor thickness and the presence of ulceration are some of the known prognostic factors used as indicators of malignant melanoma. Therefore, the discovery of valuable markers to assess the malignant potential of melanoma more accurately may be necessary to develop appropriate treatments. Cross talk between cancer cells and surrounding stromal cells is believed to orchestrate cancer progression through a variety of mechanisms. Cancer-associated fibroblasts (CAFs) - key factors in the tumor microenvironment - in particular have been implicated in cancer cell progression. It has also been reported that the exosomes, a type of small vesicles, produced by CAFs play an important role in cancer progression. A research group led by Naho Fujii, M.D., and Professor Hisashi Motomura from Osaka Metropolitan University Graduate School of Medicine investigated the effect of CAF-derived exosomes on the growth of malignant melanoma cells. The group found that the transmembrane proteins CD9 and CD63 were mainly present on CAF-derived exosomes, and that among the exosomes, the CD9-positive ones inhibited the growth of malignant melanoma cells. "As a plastic surgeon, usually I provide surgical treatment for skin cancer, but I have wanted to study other treatment methods for a long time," explained Fujii, M.D. "This study suggests that CD9-positive exosomes inhibit the growth of malignant melanoma, so CD9-positive exosomes may be a useful marker to evaluate the malignant grade of melanoma. We expect further research will lead to the development of new treatments in that line." Fujii N, Yashiro M, Hatano T, Fujikawa H, Motomura H. CD9-positive Exosomes Derived from Cancer-associated Fibroblasts Might Inhibit the Proliferation of Malignant Melanoma Cells. Anticancer Res. 2023 Jan;43(1):25-33. doi: 10.21873/anticanres.16130

Time BioVentures has set out to fund biotech companies that could balloon into Silicon Valley-like wonders. The cold war between coastal biotech hubs has taken another turn, with an amalgamation of buzzy California-based investors closing a new venture fund to stake uncharted terrain for the industry.  Time BioVentures has wrapped up its first venture fund, announcing $100 million in investments to “finance game-changing innovations in healthcare,” according to an announcement Wednesday. Arguably the most prominent of the fund's limited partners is Uber and Twitter investor Chris Sacca. The firm’s general partners are musician and Spotify investor D.A. Wallach along with former Novartis executive Tim Wright, who was most recently the chief research and development officer at Regulus Therapeutics. It’s a somewhat unlikely pairing—but the two meld early start-up experience with drug development know-how.  And judging by the fund’s unveiling, there’s no shortage of internal hype.  “This is perhaps the largest addressable market in the global economy, and we believe that the Mark Zuckerbergs and Larry Pages of healthcare are out there and will build generationally important companies that will transform medicine for decades to come," Wallach said in a release. It's probably safe to assume that Time's backers don't want to copy Zuckerberg too literally—his company Meta has lost almost two-thirds of its value in a year and Facebook is currently going through its first round of layoffs ever—but it gives a sense of the firm's willingness to look further afield for inspiration. Time’s commercial and scientific advisors include former Illumina CEO Jay Flatley, Napster founder Sean Parker and Nobel-prize-winning scientist Jim Allison, Ph.D. Time’s first investments have included Elon Musk co-founded Neuralink, which is designing an implantable “brain-computer interface” to allow people with disabilities to control computers with their brain. No, this is not a sci-fi plot. It’s also not the first time Wallach and Musk have linked up, with the former also an investor in Musk's SpaceX.  Another pet project for the firm is Amsterdam-based Kling Biotherapeutics, which last month dosed its first patient in a phase 1b trial testing its anti-CD9, KBA1412, to treat solid tumors. The open-label, dose-escalation trial is looking to recruit just more than 100 patients across the Netherlands and Belgium. Future expansion cohorts plan to test KBA1412 with PD-1 checkpoint inhibitors.