Atara Biotherapeutics Inc., of South San Francisco, said an abstract describing the preclinical safety, improved functional characteristics and antitumor efficacy of ATA-2271, a next-generation autologous CAR T-cell therapy targeting mesothelin, was selected for a late-breaking poster presentation at the second American Association for Cancer Research virtual meeting. The company has selected mesothelin as the target for both the ATA-2271 autologous and the ATA-3271 allogeneic programs along with CAR T-cell technologies to further enhance activity. Results will be presented from IND-enabling preclinical studies with ATA-2271 technologies, designed to help overcome current CAR T challenges with targeting solid tumors, including the 1XX CAR signaling domain and a dominant-negative programmed death-1 receptor (PD1DNR). In vitro, ATA-2271 exhibited antigen-specific cytotoxicity, accumulation and effector cytokine secretion, while in vivo results demonstrated that a single dose of ATA-2271 led to tumor eradication and superior survival in mice compared to mesothelin-targeted M28z CAR T cells. Mice treated with a single dose of ATA-2271 also showed sustained and persistent protection from tumor reestablishment upon 10 additional tumor re-challenges. Those data will be used to support submission of an IND with the FDA.
Avacta Group plc, of Cambridge, U.K., said several Affimer reagents generated for development of a point-of-care COVID-19 antigen saliva test have also been shown to block the interaction between the virus’ spike protein and ACE2, a receptor on human cells that is key to the virus infection pathway. The company has already generated a large number of Affimer reagents that bind to the SARS-COV-2 virus’ spike protein as part of its partnership with Cytiva (formerly GE Healthcare Life Sciences and now part of Danaher Corp). The companies are working together to develop a rapid point-of-care COVID-19 antigen saliva test to be mass produced for large-scale population screening and for self-testing by consumers.
Bioinvent International AB, of Lund, Sweden, and Transgene SA, of Strasbourg, France, are reporting new preclinical data demonstrating the broad therapeutic potential of BT-001, an anti-CTLA4 antibody-encoding oncolytic virus, against solid tumors and these data will be presented at the AACR 2020 virtual meeting II. BT-001 been engineered to encode a Treg-depleting, anti-CTLA4 antibody generated by Bioinvent. It uses Transgene’s vaccinia based viral vector platform to deliver the immunotherapy directly into the tumor. Preclinical data show therapeutic effect, indicated by curative potential as a single agent in multiple syngeneic mouse models spanning solid tumor models (CT26, EMT6, C38, and A20), as well as improved therapeutic window relative to systemic anti-CTLA4 blockade, indicated by higher, receptor-saturating, intratumoral anti-CTLA4 antibody. BT-001's activity was further enhanced when combined with anti-PD-1 antibody therapy.
Codiak Biosciences Inc., of Cambridge, Mass., said new preclinical data on programs using its Engex platform demonstrate the adaptive immune response driven by its Exovacc vaccine platform compared to standard vaccine approaches and the first data on its ability to utilize Engex to direct tropism for multiple cell types in vitro and in vivo. Those data, which were presented at the American Society of Gene & Cell Therapy meeting, demonstrate the broad potential of engineered exosomes to serve as a foundation for new classes of molecular medicines to address complex, immune-mediated diseases, the company said. It is developing exosome product candidates to target multiple pathways throughout the body to treat various forms of cancer and, through its Exovacc platform, to enhance the immune response against a broad array of antigens.
Editas Medicine Inc., of Cambridge, Mass., said results from a preclinical study evaluating multigene knockout and transgene knock-in using its engineered CRISPR/Cas12a (EngCas12a) in induced pluripotent stem cells (iPSCs) for the development of engineered cell immunotherapy medicines were presented at the American Society of Gene & Cell Therapy meeting. The results of that study further reinforce the company’s belief in the transformative potential of iPSC-derived natural killer (iNK) cells as off-the-shelf engineered cell medicines for the treatment of solid tumor cancers. In the study, CRISPR/Cas12a was used to make highly edited iPSC clones, which were then differentiated into functional iNK cells. The iNKs had enhanced tumor killing activity relative to iNKs from unedited iPSCs, demonstrating the utility of an edited iPSC platform. The company said these data support the continued development of off-the-shelf engineered cell medicines for people with solid tumor cancers.
Essa Pharma Inc., of Houston, presented new preclinical data on EPI-7386 at the virtual American Urological Association meeting. In vitro cellular gene expression analyses demonstrate that EPI-7386 inhibits androgen-induced genes with major similarities but some differences from enzalutamide in a cellular model sensitive to androgen receptor inhibitors. In the same cellular model, the combination of enzalutamide and EPI-7386 inhibited androgen-induced gene expression more completely and broadly. EPI-7386 showed superiority to enzalutamide in inhibiting androgen-induced genes in an androgen receptor resistant model, and in contrast to enzalutamide, also blocks genes induced by the AR-V7 androgen receptor splice variant. The drug was well-tolerated at both the low and middle doses, corresponding to drug plasma exposures twofold to fivefold higher than the efficacious exposures achieved in mouse xenograft models.
Exvastat (Ireland) Ltd., of Dublin, said the Innovative Medicines Initiative has, through a competitive process, awarded the company a €3.6 million (US$3.89 million) grant, following its call for developers to uncover a new use of the licensed drug therapy imatinib for the treatment of acute respiratory distress syndrome (ARDS) induced by COVID-19. Under this award, Exvastat will collaborate with Vrije Universitat, Amsterdam Medical Center, KABS (Canada) and Simbec-Orion to produce a reformulated version of the drug and test it in critically ill COVID-19 patients. The trial will investigate the potential benefit to COVID-19 patients who lack any approved therapeutic options. The trial is expected to enroll 110 COVID-19 patients following a four- to six-month reformulation program. Unlike antiviral approaches, imatinib operates through the inhibition of the host response, reducing the pulmonary edema that is correlated with mortality in all forms of ARDS, and is therefore anticipated to be a robust mechanism against viral mutations.
Halozyme Therapeutics Inc., of San Diego, said it will receive a $15 million milestone payment from New Brunswick, N.J.-based Johnson & Johnson’s Janssen Biotech unit. The payment was triggered under the collaboration and license agreement between the two companies. The milestone payment is associated with the first commercial sale in the U.S. of Darzalex Faspro (daratumumab and hyaluronidase-fihj) utilizing Enhanze delivery technology.
Hifibio Therapeutics Inc., of Cambridge, Mass., generated preclinical data packages for monoclonal antibodies that demonstrate favorable clinical development profiles as new cancer immunotherapeutic options. The team will present highlights in three poster sessions at the forthcoming American Association for Cancer Research meeting, held virtually. HFB-301001, a fully human IgG1 class OX-40 agonistic antibody, has shown that, in contrast to previous anti-OX-40 antibodies, it is further enhanced in the presence of the endogenous ligand OX-40L, does not result in reduced expression of OX-40 on T cells, and leads to superior antitumor activity in a human OX-40 knock-in mouse model compared to a benchmark antibody. Data from its HFB-2003 program show the anti-TNFR2 monoclonal antibody had comparable single-agent antitumor activity to anti-PD-1 in several mouse tumor models at well-tolerated doses. The company also has HFB-2009, which targets galactoside-binding lectin Galectin 9, which demonstrated antitumor activity and increased survival as a single agent and in combination with anti-PD-1 in a syngeneic tumor model.
Lava Therapeutics BV, of Utrecht, the Netherlands, said it entered a research and license agreement with New Brunswick, N.J.-based Johnson & Johnson’s Janssen Biotech unit to discover and develop bispecific antibodies to gamma-delta T cells for the treatment of cancer. Lava will perform discovery and product development activities and is eligible to receive an undisclosed financial package consisting of an up-front payment and potential development and commercial milestone rewards, as well as tiered royalties.
Legochem Biosciences Inc., of Daejeon, South Korea, disclosed a worldwide license agreement with Iksuda Therapeutics Ltd., of Newcastle, U.K., for the development and commercialization of LCB-73, a CD19-targeted antibody-drug conjugate candidate for hematological tumors. Iksuda will make an up-front payment of $5 million, and Legochem is eligible to receive development, regulatory and commercial milestone payments of up to $222 million as well as royalties. Legochem is also entitled to receive a prearranged percentage of sublicense revenue if Iksuda enters license agreement with third-party companies.
Mirror Biologics Inc., of Phoenix, Ariz., and Immunovative Therapies Ltd., of Jerusalem, with the Hadassah-Hebrew University Medical Center’s Center for Immunotherapy and Immunobiology Research, disclosed the publication of a manuscript describing the scientific rationale for a new approach for vaccine development for the elderly. The patent-pending technology called Allopriming is designed so that a series of injections of bioengineered cells, called Allostim, could provide protection from any future viral infection, including COVID-19, influenza and any future mutations of those viruses or an outbreak of a new novel virus. The technology proposes to prime the elderly immune system to respond to viruses in the same manner as a healthy younger adult immune system would respond, the companies said. The manuscript was published online in the Journal of Translational Medicine.
Nantkwest Inc., of El Segundo, Calif., and Culver City, Calif.-based Immunitybio Inc. said that in June they expect to begin a phase II, randomized, open-label study to evaluate their combination immunotherapy, comprising Nantkwest’s PD-L1 tumor-targeted natural killer cells and Immunitybio’s IL-15 superagonist N-803, and aldoxorubicin HCI plus standard of care, vs. standard-of-care chemotherapy for first- and second-line treatment of locally advanced or metastatic pancreatic cancer.
The NIH has started a clinical trial to evaluate whether the malaria drug hydroxychloroquine, given together with the antibiotic azithromycin, can prevent hospitalization and death from COVID-19. The study will enroll about 2,000 adults with confirmed infection with SARS-CoV-2 infections, assigning them to at-home dosing of either the active or a matching placebo-based regimen. Those in the active arm will take 400 mg of hydroxychloroquine twice on the first day and 200 mg twice daily for six additional days. They'll also take 500 mg of azithromycin on the first day and 250 mg daily for an additional four days. The study, being conducted by the NIAID-funded AIDS Clinical Trials Group, is called A5395. Teva Pharmaceutical Industries Ltd., of Jerusalem, is donating medications for the trial.
Nimbus Therapeutics Inc., of Cambridge, Mass., said it has identified a small-molecule inhibitor of HPK1 (hematopoietic progenitor kinase 1) that, in a mouse syngeneic tumor model, "completely eliminated HPK1’s phosphorylation of the T-cell receptor, enhanced inflammatory cytokine production, and demonstrated robust tumor growth inhibition." The company is now advancing the program into IND-enabling studies, with the goal of entering the clinic next year. Further information about the molecule will be presented as part of the upcoming American Association for Cancer Research meeting, to be held June 22-24.
Omass Therapeutics Ltd., of Oxford, U.K., highlighted the publication in Nature Methods of an article describing a new top-down mass spectrometry approach developed in collaboration with researchers from Oxford University, the Karolinska Institute and Thermo Fisher Scientific Inc. The development allows definition of the lipidome/metabolome in contact with the protein complex of interest, the company said.
Rapt Therapeutics Inc., of South San Francisco, reported preclinical data at the Society for Investigative Dermatology meeting showing that, in multiple preclinical studies of allergic skin inflammation, once-daily dosing of CCR4-targeting small-molecule RPT-193 demonstrated efficacy and reduction of Th2 cytokines comparable to treatment with currently available biologics that work by blocking interleukin-4 (IL-4) and IL-13, the major drivers of allergic inflammatory disease.
Roche Holding AG, of Basel, Switzerland, has become a founding partner of Baselaunch, a Basel area-based incubator and accelerator that helps scientists and entrepreneurs launch new biotech companies. Additional partners will be made public over the coming months, the incubator said.
Rubius Therapeutics Inc., of Cambridge, Mass., said preclinical data have shown that its artificial antigen-presenting cells (aAPC) can activate and expand tumor-specific T cells in vivo and stimulate production of key antitumor effector molecules, leading to tumor control. Its aAPC candidate, RTX-321, "similarly activates and expands HPV16-specific human T cells in vitro to become immune-effector cells," suggesting that it may lead to durable responses in patients with HPV16-positive cancers, the company said. Plans are laid for an IND filing by year-end.
Silverback Therapeutics Inc., of Seattle, plans to present preclinical data on SBT-6050, a monoclonal antibody targeting HER2 conjugated to a TLR8 agonist, at the ASCO20 Virtual Scientific Program and AACR 2020 Virtual Annual Meeting. In preclinical models, activation of myeloid cells resulted in single-agent antitumor immune responses, even in tumors lacking T cells.
Sorrento Therapeutics Inc., of San Diego, said its anti-SARS-CoV-2 antibody, STI-1499, demonstrated 100% inhibition of SARS-CoV-2 virus infection in an in vitro virus infection experiment at a very low antibody concentration. As recently announced, Sorrento said it aims to generate an antibody cocktail product that would act as a "protective shield" against SARS-CoV-2 coronavirus infection and remain effective even if virus mutations render a single antibody therapy less effective over time. Sorrento has determined STI-1499 will likely be the first antibody in the antibody cocktail and is also expected to be developed as a stand-alone therapy. Shares of Sorrento (NASDAQ:SRNE) shot up 158% to close May 15 at $6.76, up $4.14.
Syntekabio Inc., of Daejeon, South Korea, reported preclinical results for STB-C017, an inhibitor of IDO and TDO, showing the drug blocked kynurenine secretion from tumors in colorectal cancer mouse models. The drug increased infiltration of CD8+ T cells into the tumor and reduced regulatory T cells. Treatment with STB-C017 plus anti-PD-1 and anti-CTLA4 antibodies delayed tumor growth and produced twice as many complete responses as epacadostat plus the two antibodies. The data will be presented at the 2020 American Association for Cancer Research annual meeting.
TG Therapeutics Inc., of New York, reported preclinical data for its BTK inhibitor, TG-1701, showing that the drug didn't inhibit anti-CD20 antibody-dependent cellular cytotoxicity and phagocytosis of rituximab in a multicellular co-culture system that associated mantle cell lymphoma (MCL) to effector cells. TG-1701 plus an anti-CD20 antibody, ublituximab, and a PI3Kdelta-CK1epsilon dual inhibitor, umbralisib, reduced tumor growth in both ibrutinib-sensitive (REC1) and ibrutinib-resistant (UPN-1res) mouse models of MCL. The data will be presented at the 2020 American Association for Cancer Research annual meeting.
Theratechnologies Inc., of Montreal, reported preclinical data for its sortilin-targeting peptide-drug conjugates, TH-1901, TH-1902 and TH-1904, to be presented at the 2020 American Association for Cancer Research annual meeting. TH-1901, which is conjugated to curcumin, reduced proliferation of cancer cells by more than 100 times compared to curcumin. TH-1902, which is conjugated to docetaxel, inhibited vasculogenic mimicry in a triple-negative breast cancer model. TH-1904, which is conjugated to doxorubicin, stopped the formation of vasculogenic mimicry in an ovarian cancer model.
Transgene SA, of Strasbourg, France, and NEC Corp., of Tokyo, reported data on the prediction algorithm used to customize TG-4050 tumor vaccine for each patient, demonstrating that it's accurate at identifying immunogenic cancer mutations. The data will be presented at the 2020 American Association for Cancer Research annual meeting.
Tyme Technologies Inc., of New York, reported preclinical data on two cancer metabolism-based therapies, SM-88 and TYME-18, to be presented at the 2020 American Association for Cancer Research annual meeting. SM-88 reduced tumor size as compared to control mice. The drug increases oxidative stress from reactive oxygen species, interferes with autophagy and modulates tumor immunity by reducing immunosuppressive macrophages. TYME-18 produced complete tumor regression in animal tumor models.
Vividion Therapeutics Inc., of San Diego, reported the discovery of drugs capable of covalently engaging E3 ligases and driving targeted degradation, which will be presented at the 2020 American Association for Cancer Research annual meeting. Several molecules were able to degrade more than 50% of their target proteins at doses less than 1 mg/kg in mice.
Vsy Biotechnology GmbH, of Leinfelden-Echterdingen, Germany, reported the discovery of TR-C 19, which is capable of neutralizing the coronavirus that causes COVID-19 in vitro. The company plans to move the drug into clinical development.
Xencor Inc., of Monrovia, reported preclinical data on three 2+1 bispecific antibody programs and an IL-12-Fc cytokine program, which will be presented at the 2020 American Association for Cancer Research annual meeting. XmAb-30819, which targets ENPP3 and CD3, had in vivo efficacy in models for renal cell carcinoma. A PSMA x CD3 bispecific antibody had activity in prostate cancer models. A bispecific antibody targeting mesothelin and CD3 directed T cells to ovarian cancer cells. And the IL-12 heterodimeric Fc-fusion proteins had antitumor activity.