PARPBP

Pictured: Gilead sign in front of building/courtesy of Tada Images/Shutterstock Tuesday, a Delaware jury ruled in favor of Gilead Sciences, finding that the company’s HIV prevention medicines Truvada (emtricitabine/tenofovir disoproxil fumarate) and Descovy (emtricitabine/tenofovir alafenamide) do not infringe on U.S. government patents and that the patents themselves are invalid in the first place. Three patent claims were at the core of the lawsuit. Jurors overwhelmingly took Gilead’s side and found that the government failed to provide enough evidence showing that patients or physicians violated these patent protections by using Truvada or Descovy for pre-exposure prophylaxis (PrEP) for HIV. Meanwhile, the jury found that Gilead had been able to show “clear and convincing evidence” that all three patent claims were invalid. Truvada is a combination of two inhibitors of the HIV-1 reverse transcriptase enzyme. It prevents the virus from integrating its genetic material into its host and replicating inside the patient’s body. The drug was first approved in 2004 for the treatment of HIV-1 and then again in July 2012 for use as PrEP. Like Truvada, Descovy combines two HIV reverse transcriptase inhibitors and works via a similar mechanistic pathway. It was first approved in 2016 for HIV treatment and won another regulatory nod in October 2019 for prevention. A month later, in November 2019, the Trump administration, through the Department of Human and Health Services (HHS), sued Gilead over these PrEP approvals. The government alleged that the drug regimen that Truvada and Descovy use was first invented and proposed for prophylaxis by CDC researchers in the early 2000s. “Gilead has received billions of dollars in revenue from HIV prevention regimens invented by HHS researchers and patented by the United States,” said Jody Hunt, the Department of Justice’s assistant attorney general for the civil division in a 2019 statement. Cancer, Inflammatory Disease Deal Also on Tuesday, Gilead announced it was acquiring private San Diego biotech XinThera but declined to disclose the deal’s financial details. The buyout will give Gilead rights to XinThera’s small molecule inhibitors targeting the PARP1 protein for oncology indications and the MK2 protein for inflammatory diseases. Both PARP1 and MK2 programs have candidates that could enter clinical trials later this year and could also be leveraged to address other conditions, with the potential for combination treatments with other molecules in Gilead’s portfolio. XinThera’s highly selective PARP1 inhibitors bypass the hematological toxicities typically seen with first-generation dual PARP1/2 inhibitors. This could potentially enable combo treatments with DNA-damaging agents such as Gilead’s own Trodelvy (sacituzumab govitecan-hziy), which delivers a toxic payload into cancer cells to induce cell death. Trodelvy was first approved in 2020 for metastatic triple-negative breast cancer. Tristan Manalac is an independent science writer based in metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

Courtesy of Tada Images/Getty Images The biopharma company scored two major wins on Tuesday: a court victory over HIV patent claims and an acquisition deal to expand its pipeline in cancer and inflammatory diseases. Pictured: Gilead sign in front of building/courtesy of Tada Images/Shutterstock Tuesday, a Delaware jury ruled in favor of Gilead Sciences , finding that the company’s HIV prevention medicines Truvada (emtricitabine/tenofovir disoproxil fumarate) and Descovy (emtricitabine/tenofovir alafenamide) do not infringe on U.S. government patents and that the patents themselves are invalid in the first place. Three patent claims were at the core of the lawsuit . Jurors overwhelmingly took Gilead’s side and found that the government failed to provide enough evidence showing that patients or physicians violated these patent protections by using Truvada or Descovy for pre-exposure prophylaxis (PrEP) for HIV. Meanwhile, the jury found that Gilead had been able to show “clear and convincing evidence” that all three patent claims were invalid. Truvada is a combination of two inhibitors of the HIV-1 reverse transcriptase enzyme. It prevents the virus from integrating its genetic material into its host and replicating inside the patient’s body. The drug was first approved in 2004 for the treatment of HIV-1 and then again in July 2012 for use as PrEP. Like Truvada, Descovy combines two HIV reverse transcriptase inhibitors and works via a similar mechanistic pathway. It was first approved in 2016 for HIV treatment and won another regulatory nod in October 2019 for prevention. A month later, in November 2019, the Trump administration, through the Department of Human and Health Services (HHS), sued Gilead over these PrEP approvals. The government alleged that the drug regimen that Truvada and Descovy use was first invented and proposed for prophylaxis by CDC researchers in the early 2000s. “Gilead has received billions of dollars in revenue from HIV prevention regimens invented by HHS researchers and patented by the United States,” said Jody Hunt, the Department of Justice’s assistant attorney general for the civil division in a 2019 statement . Cancer, Inflammatory Disease Deal Also on Tuesday, Gilead announced it was acquiring private San Diego biotech XinThera but declined to disclose the deal’s financial details. The buyout will give Gilead rights to XinThera’s small molecule inhibitors targeting the PARP1 protein for oncology indications and the MK2 protein for inflammatory diseases. Both PARP1 and MK2 programs have candidates that could enter clinical trials later this year and could also be leveraged to address other conditions, with the potential for combination treatments with other molecules in Gilead’s portfolio. XinThera’s highly selective PARP1 inhibitors bypass the hematological toxicities typically seen with first-generation dual PARP1/2 inhibitors. This could potentially enable combo treatments with DNA-damaging agents such as Gilead’s own Trodelvy (sacituzumab govitecan-hziy), which delivers a toxic payload into cancer cells to induce cell death. Trodelvy was first approved in 2020 for metastatic triple-negative breast cancer. Tristan Manalac is an independent science writer based in metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com .

It was another busy week for clinical trials. Here’s a look. It was another busy week for clinical trials. Although not exclusively, a lot of results came out of the European Society of Medical Oncology Congress (ESMO) held in Barcelona, Spain from September 27 through October 1. Here’s a look. The University of Texas MD Anderson Cancer Center published results from its BEACON CRC Phase III clinical trial of 665 patients with BRAF V600E-mutated metastatic colorectal cancer who had disease progression after one or two previous treatments. Patients received either a triplet therapy of encorafenib, binimetinib, and cetuximab or a doublet therapy of encorafenib and cetuximab, or the investigators’ choice of either cetuximab and irinotecan or cetuximab and FOLFIRI (folinic acid, fluorouracil, and irinotecan), the control group. The median overall survival (OS) in the triplet group was 9 months, 5.4 months for the control group, and 8.4% in the doublet group. SkylineDx announced validation of its skin cancer (melanoma) diagnostic test on the first, independent European dataset. The test uses genetic information from a patient’s tumor cells with patient-specific characteristics. The test accurately predicted the risk of metastases in the lymph nodes without a patient requiring surgery to remove part of the lymph nodes. Stemedica reported positive results from the Phase IIa clinical trial of its IV infusion of allogeneic ischemia-tolerant mesenchymal stem cells (MSC) in chronic stroke. The primary outcome was safety based on behavior, CT scans and lab results. Secondary endpoints were related to a variety of behavioral changes, including neurological assessments, daily tasks, mental status and depression. Ayala Pharmaceuticals presented encouraging preliminary results from its ongoing Phase II ACCURACY trial of AL101 in patients with recurrent/metastatic adenoid cystic carcinoma (ACC) with progressing disease and Notch activating mutations. AL101 is an investigational small molecule, gamma-secretase inhibitor that selectively inhibits Notch 1, 2, 3 and 4. There are currently no standard drug therapies for ACC. Checkpoint Therapeutics announced positive interim results for its ongoing Phase I trial of cosibelimab in cutaneous squamous cell carcinoma (CSCC) and non-small cell lung cancer (NSCLC). Cosibelimab is a differentiated high affinity anti-PD-L1 antibody with functional Fc domain. So far, in the CSCC cohort there was a 50% objective response rate (ORR) and in the NSCLC cohort a 40% ORR. Tyme presented supporting data of its Phase II TYME-88-Panc trial of SM-88 (racemetyrosine) as an oral monotherapy in patients with advanced pancreatic cancer. It showed encouraging overall survival (OS) results and a well-tolerated safety profile. The company also presented data from its Phase II trial of SM-88 in patients with non-metastatic, biochemical-recurrent prostate cancer that were positive. hbspt.cta.load(4413123, '4e87abe9-779b-4c65-98dd-ea451779faa9', {}); ORYZON Genomics released additional data from CLEPSIDRA, its ongoing Phase II trial of iadademstat in combination with standard-of-care in relapsed extensive disease (ED) small cell lung cancer (SCLC). The combination showed promising clinical efficacy with 6 of 8 patients. There were 4 partial remissions and 2 long-term disease stabilizations. Iadademstat is an inhibitor of the epigenetic enzyme LSD1. It also released data on its central nervous system epigenetic drug vafidemstat. This was from three different cohorts of psychiatric patients in the Phase II REIMAGINE trial: attention deficit hyperactivity disorder (ADHD), autistic spectrum disorder (ASD) and borderline personality disorder (BPD). Cellectar Biosciences announced data from the diffuse large B-cell lymphoma (DLBCL) cohort in its Phase II CLOVER-1 trial of CLR 131 in relapsed or refractory select B-cell malignancies. Interim data showed durable responses, including a 33% ORR, a 16.6% complete response rate (CR) and a 50% clinical benefit rate (CBR). Tarveda Therapeutics presented data from the Phase I part of its Phase I/IIa clinical trial of PEN-866 for a variety of solid tumors. Early evidence showed the drug was well tolerated and had anti-tumor activity. PEN-866 is a small molecule miniature drug conjugate linked to a potent topoisomerase 1 inhibitor (SN-38) payload that targets and binds to Heat Shock Protein 90 (HSP90). Adaptimmune updated data from its ongoing Phase I trial with SPEAR T-cells targeting MAGE-A4 in synovial sarcoma. The data showed a clear benefit. “These results are truly meaningful in this rare and deadly disease because patients with advanced synovial sarcoma have very few treatment options,” said Elliot Norry, the company’s interim chief medical officer. “These data and the recent FDA orphan drug designation for ADP-A2M4 in sarcoma are important positive steps to expedite further development.” AstraZeneca and Merck presented results from the Phase III PROfound trial in metastatic castration-resistant prostate cancer (mCRPC) who have a mutation in their homologous recombination repair (HRR) genes and whose disease has progressed on previous treatment with abiraterone or enzalutamide. The trial showed a statistically significant and clinically meaningful improvement with Lynparza in the primary endpoint of radiographic progression-free survival (rPFS) in BRCA1/2 or ATM-mutated tumors reducing the risk of disease progression or death by a median of 7.4 months versus 3.6 months. Rakuten Medical released post-hoc analysis of safety, pharmacokinetic, immunogenicity and exploratory biomarker data from its RM-1929 photoimmunotherapy (PIT) Phase I and I/IIa studies. They evaluated the safety and anti-tumor activity of RM-1929 PIT in patients with locoregional, recurrent head and neck squamous cell carcinoma (rHNSCC). They reported clinically meaningful anti-tumor activity and a positive safety profile. Zai Lab ’s partner, GlaxoSmithKline , released results from PRIMA, the Phase III trial of niraparib as a monotherapy for the first-line maintenance of platinum responsive advanced ovarian cancer. Niraparib is a PARI inhibitor. The treatment resulted in a 38% reduction in the risk of disease progression or death in the overall population. TLC , a special pharma company, initiated a Phase III trial of TLC599 in osteoarthritis of the knee. TLC599 is a BioSeizer sustained release formulation of dexamethasone sodium phosphate (DSP). The trial, EXCELLENCE, is a multi-center, randomized, double-blind, placebo- and active comparator-controlled pivotal trial that will look at about 500 patients with knee osteoarthritis at 40 to 50 sites in the U.S. and Australia. Octernal Therapeutics opened a Phase Ib expansion cohort of its trial of cirmtuzumab in combination with ibrutinib in mantle cell lymphoma. Cirmtuzumab is a ROR1-targeted monoclonal antibody. Ibrutinib is marketed by Johnson & Johnson as Imbruvica. Catalyst Biosciences updated enrollment on its Phase IIb trial of dalcinonacog alfa (DalcA). DalcA is a next generation subcutaneously (SQ) administered Factor IX therapy being developed for hemophilia B. Two subjects completed dosing and washout, and Factor IX levels exceeded the trial efficacy endpoint. Enrollment is ongoing. Catalyst expects final data in the first half of 2020. Heron Therapeutics announced positive topline results from its Phase IIIb trial of HTX-011 in total knee arthroplasty (TKA). The trial showed the drug significantly reduced pain and opioid use compared to placebo through 72 hours and significantly decreased pain compared to bupivacaine solution, the standard-of-care local anesthetic for postoperative pain control. HTX-011 is a dual-acting, fixed-dose combination of bupivacaine with a low dose of the nonsteroidal anti-inflammatory meloxicam. Novartis reported positive final results from its Phase III trial of Cosentyx for non-radiographic axial spondyloarthritis (nr-axSpA). The drug showed a significant and clinically meaningful decrease in disease activity compared to placebo. This included a sustained response and consistent safety pro 52 weeks. Eli Lilly presented data from its Phase IV IXORA-R trial, a head-to-head study of an IL-17A inhibitor and an IL-23/p19 inhibitor in plaque psoriasis. In the trial, Lilly’s Taltz (ixekizumab) showed superiority to Johnson & Johnson’s Tremfya (guselkumab) in patients with moderate to severe plaque psoriasis. The primary endpoint was superiority in the proportion of patients with moderate to severe plaque psoriasis achieving complete skin clearance as measured by the Psoriasis Area Severity Index (PASI) 100 at Week 12. Sarepta Therapeutics announced the nine-month functional data from three Limb-girdle muscular dystrophy Type 2E (LGMD2E) patients who received SRP-9003. The therapy is a gene therapy that transduces skeletal and cardiac muscle with a gene that codes for the full-length, native beta-sarcoglycan protein, whose absence causes LGMD2E. All three patients showed improvements on functional measures and a significant decrease in creatine kinase that was maintained over nine months. hbspt.forms.create({ portalId: "4413123", formId: "a126e976-bca0-4c13-aa9b-02e8feb92096" });