Parathyroid Hormone(Shire Plc)

Cancers of the head and neck can be treated with several drugs on the market, but for certain patients diagnosed with this this common type of cancer, outcomes are worse and better therapeutic options are needed. Bicara Therapeutics is developing a therapy that could provide a treatment alternative and the company now has $315 million in IPO cash to finance a pivotal study. Boston-based Bicara was able to raise more than it planned. In preliminary IPO terms set on Monday, the company aimed to offer 11.7 million shares priced in the range of $16 to $18 each. On Wednesday, Bicara increased the proposed stock sale to 14.7 million shares offered in the same targeted price range. When shares finally priced late Thursday, Bicara boosted the deal size yet again, offering 17.5 million shares for $18 each, right at the top of the targeted price range. Those shares now trade on the Nasdaq under the stock symbol “BCAX.” Most head and neck squamous cell carcinoma (HNSCC) cases come from exposure to carcinogens such as tobacco smoke or from human papillomavirus (HPV), Bicara says in its IPO filing. That virus can lead to cellular changes that over time, become precancerous and then cancerous. However, an estimated 80% of recurrent or metastatic HNSCC cases are HPV-negative. These tumors are associated with an increased risk of fatal tumor bleeding, excruciating pain, and difficulty swallowing. Sponsored Post What Healthcare Can Learn from Costco The path forward is clear: employers must evaluate their health plan the same way they do their Saturday shopping excursion. By Jeff Bak, Imagine360 CEO and President Bicara’s drugs are antibodies engineered to address solid tumors by hitting two validated cancer targets. The company’s lead program, ficerafusp alfa, is a bifunctional antibody drug designed to bind to epidermal growth factor receptor (EGFR) and human transforming growth factor beta (TGF-beta). TGF-beta is an important target because high signaling from this protein is associated with resistance to the class of immunotherapies called checkpoint inhibitors. For that reason, drugs that hit this target have been tested as a way to potentially overcome this resistance. GSK and Merck KGaA tried this approach with a bifunctional protein, bintrafusp alfa. But clinical trial results showed the experimental therapy fell short on measures of efficacy. In its IPO filing, Bicara said such failures may be due to insufficient anti-tumor activity, possibly because the immunotherapy is being expressed in immune tissue rather than the tumor microenvironment (TME) where it’s needed. Bicara says the dual approach of its drug blocks survival signaling from EGFR as well as immunosuppressive TGF-beta signaling in the TME. Bicara has been testing its experimental drug in combination with the blockbuster Merck immunotherapy pembrolizumab, brand name Keytruda, whose approved indications include HNSCC. An ongoing Phase 1/1b study of the Bicara drug includes a group of HNSCC patients who had not previously received treatment after their cancer had advanced. In this cohort, Bicara said the combination of the study drug and Keytruda led to a 54% overall response rate in patients who could be evaluated for efficacy. In patients whose disease was HPV negative, the overall response rate was 64%. For context, the historical response rate in a Phase 3 test of Keytruda monotherapy in HNSCC was 19%, the company said in the filing. The company expects to report more Phase 1/1b data at a medical meeting in 2025. “Based on the clinical data generated to date, we believe that ficerafusp alfa in combination with pembrolizumab has the potential to become a first-line standard of care therapy in HPV-negative [recurrent/metastatic] HNSCC,” Bicara said in the filing. “We also believe ficerafusp alfa has the potential to provide meaningful clinical benefit in other solid tumors where there is a strong biologic rationale for the dual inhibition of both EGFR and TGF-beta, such as colorectal cancer and other squamous cell carcinomas which typically overexpress EGFR and TGF-beta pathways.” presented by Sponsored Post The Promise of Value-Based Care and MedTech Innovation Monica Vajani, Executive Director for mHUB’s MedTech Accelerator, discusses how mHUB is helping innovators transition healthcare towards value-based care. By Monica Vajani - mHUB A pivotal Phase 2/3 clinical trial is planned that will test the Bicara therapy in combination with the Merck immunotherapy pembrolizumab, brand name Keytruda, as a first-line treatment for advanced HNSCC. Bicara expects this study will start by the end of this year or in the first quarter of 2025. Bicara formed in 2018. The following year, the company licensed certain fusion proteins from Biocon Limited. The most advanced of those fusion proteins was ficerasfusp alfa. There are no future milestone payments or royalties tied to the deal, Bicara said in the filing. The prospectus says Bicara has raised $353.1 million since its inception. The most recent financing was a $165 million Series C round announced last December. Biocon is Bicara’s largest shareholder, owning an 11.28% post-IPO stake, according to the filing. RA Capital Management owns a 10.5% stake after the IPO. As of the end of the second quarter of this year, Bicara reported a cash position of $203.9 million. Combined with the IPO proceeds, the company plans to spend about $265 million on the development of ficerafusp alfa in HNSCC, including the pivotal study and the filing of a biologics license application. Another $30 million is earmarked for the expansion of its lead drug candidate in additional HNSCC patient groups. And $25 million is set aside for advancing clinical development of the drug in additional types of solid tumors, such as colorectal cancer and other squamous cell carcinomas. Zenas’s IPO Pulls in $225M for Pipeline in a Product Opportunity in I&I Zenas Biopharma, a company developing antibody drugs to treat immunology and inflammation (I&I) disorders, raised $225 million. The company late Thursday priced more than 13.23 million shares at $17 each. When Zenas set preliminary financial terms this week, it aimed to offer 11.76 million shares in the range of $16 to $18 apiece, which would have raised $199.9 million at the pricing midpoint. Zenas’s shares will trade on the Nasdaq under the stock symbol “ZBIO.” Excessive activity of B cells, a type of immune cell, is associated with a range of autoimmune disorders. While antibody drugs are currently available that treat these conditions by depleting B cells, Zenas contends they don’t fully affect B cells in relevant tissue and the dosing regimen of these therapies can be improved. Another concern is that antibody drugs that target and block the proteins CD19 and CD20 on B cells may deplete these cells for six months or longer, which raises the risk of infection and could reduce a patient’s ability to respond to and benefit from vaccines. Zenas’s lead drug candidate is obexelimab, a bifunctional antibody designed to bind to CD19 and Fc gamma receptor IIb, both targets that are broadly expressed on B cells. According to Zenas, this approach mimics a natural antigen-antibody complex for inhibiting B cells. This mechanism of action is intended to inhibit the activity of B cells without completely depleting them. Zenas acquired global rights to obexelimab from Xencor in 2021. The company had previously licensed other programs from Xencor; those programs are still preclinical. While Zenas believes obexelimab has broad potential in I&I, the company is initially focusing on four indications: immunoglobulin G4-related disease (IgG4-RD), multiple sclerosis, systemic lupus erythematosus, and warm autoimmune hemolytic anemia (wAIHA). Zenas’s drug is furthest along in IgG4-RD, a chronic inflammatory condition that affects multiple organs. Standard of care includes corticosteroids. Roche’s CD20-targeting antibody drug, Rituxan, can also be used to treat the condition. Zenas is continuing a Phase 3 test of its lead drug in IgG4-RD. Since inception, Zenas said it had raised $358.3 million from investors. The company’s most recent financing was a $200 million Series C round in May led by SR One. That investor owns a 7% post-IPO stake in Zenas, according to the filing. Xencor is Zenas’s largest shareholder with an 8.1% post-IPO stake. As of the end of June, Zenas reported having $183.9 million in cash. That capital, along with the IPO proceeds, will broadly support the advancement of obexelimab. Zenas plans to spend about $100 million on clinical development of the drug, including the completion of a Phase 3 study in patients with IgG4-RD. This drug candidate will also be evaluated in separate Phase 2 tests in multiple sclerosis, lupus, and wAIHA. The company expects its capital will last for the next two years. MBX Bio’s Longer-Acting Peptide Drugs Land $163M for Clinical Trials MBX Biosciences’ IPO raised $163 million for a pipeline that includes a lead program in the clinic for a rare hormone deficiency with few FDA-approved treatments. Carmel, Indiana-based MBX priced its offering of 10.2 million shares at $16 each, which was the top of $14 to $16 per share price range it set earlier this week. The company was able to boost the deal size, offering 1.7 million more shares than it had initially planned. MBX’s shares will trade on the Nasdaq under the stock symbol “MBX.” MBX’s drugs come from a platform technology that engineering peptides with a longer duration of action that enables less frequent dosing intervals. This technology is based on research from Indiana University. Lead program MBX 2109 is a potential treatment for chronic hypoparathyroidism, a condition in which the parathyroid glands do not produce enough parathyroid hormone to regulate levels of calcium and phosphate in the blood. The first FDA-approved therapy for this condition is Takeda Pharmaceutical’s Natpara, an engineered version of the hormone. But Takeda has said it will stop offering Natpara due to ongoing manufacturing problems. Patients have a new alternative following FDA approval last month of Ascendis Pharma’s Yorvipath, a peptide injected once-daily to bring parathyroid hormone levels within the normal range. With MBX 2109, MBX aims to offer chronic hypoparathyroidism patients less burdensome once-weekly dosing. In Phase 1 testing, the company reported its engineered peptide achieved parathyroid hormone levels comparable to those achieved by a continuous infusion. A Phase 2 study dosed its first patient last month; preliminary data are expected in the third quarter of next year. Another engineered peptide, MBX 1416, in Phase 1 development for post-bariatric hypoglycemia (PBH). In this rare condition, bariatric surgery patients go on to develop dangerously low blood sugar levels. There are no FDA-approved therapies for this rare condition, but MBX isn’t alone in the pursuit for one. Amylyx Pharmaceuticals picked up its Phase 3-ready PBH peptide drug from the bankruptcy auction of Eiger BioPharmaceuticals. Another engineered peptide, MBX 4291, is in preclinical development for obesity. According to the IPO filing, MBX’s cash position at the end of June was $55.3 million. That capital, along with the IPO proceeds, will support clinical trials. MBX plans to spend $148.6 million to take its lead program through mid-stage development and into Phase 3 testing in chronic hypoparathyroidism and to advance its PBH drug through Phase 1 and Phase 2 testing. Another $31.2 million is set aside to advance the obesity program into the clinic.

Labor Day marks the unofficial end of summer, and children who haven’t already started school will be returning to classrooms soon. Because many children suffer from food allergies, EpiPens have become a staple in schools, standing ready to quickly administer an epinephrine injection to counteract an allergic reaction. This academic year, children will have an alternative. The FDA in August approved the first nasal spray epinephrine, a product from ARS Pharma that will be marketed as neffy. The regulatory decision for the 2 mg spray covers the treatment of type I allergic reactions, which includes reactions caused by food, medications, and insect bites. It may be used by adults as well as children who weigh 30 kilograms (66 pounds) or more. San Diego-based ARS said an application seeking to expand the approval to children weighing less than 30 kg is on track for an FDA submission by the end of this year. Injectable epinephrine for type 1 allergic reactions has been around since 1987. ARS developed neffy as an aqueous formulation of epinephrine and an ingredient that improves its bioavailability — how much of a drug is available to provide its effect when it is administered intranasally. The new approval comes nearly a year after the FDA turned down ARS’s application for neffy. ARS’s submission had relied on human factor studies that tested how people interact with the drug/device. The FDA asked for more clinical data. sponsored content Integrated Enrollment Platforms and Consumer Assistance Centers: The Strongest Advantage for State-Based Exchanges In the ever-evolving landscape of state-based health insurance exchanges, the convergence of technology and customer service is reshaping how these exchanges operate. The increasing advent of automation and artificial intelligence (AI) is rapidly dismantling the traditional business model that relies on the siloing of technology and customer service centers. By Shankar Srinivasan, Co-Founder and General Manager, GetInsured and Jason Sparks, VP, of Project Management and Implementation, GetInsured Neffy’s August approval came nearly two months ahead of the October target date for a regulatory decision, which William Blair analyst Tim Lugo said was expected after the FDA told ARS that it intended to move quickly on the review and the agency was under “significant pressure from patient advocacy groups” after last year’s rejection of the application. “We view the early approval as a positive ahead of the return-to-school season when many patients are expected to renew prescriptions,” Lugo said in a research note sent to investors. Lugo said ARS sees market opportunity in patients who will switch to neffy from a currently available epinephrine product as well as patients who have let their epinephrine prescriptions lapse, including those unwilling to carry or use a needle product. Longer term, the company see opportunity in tapping into an estimated 13.5 million people who have been diagnosed with a condition that could be treated with epinephrine but have not yet received a prescription. In an investor presentation, ARS said it expects to launch neffy later in the current quarter. Last week, the company announced European Commission approval of the nasal spray. ARS said this product, which will be sold in Europe under the brand name EURneffy, will launch by the end of this year. EURneffy will be marketed by another company with an already established commercial footprint in Europe. sponsored content 5 Health Reasons to Ditch Concrete Jungles for Countryside In an increasingly urbanized world, the allure of countryside living is growing stronger, especially when it comes to health and well-being. By Impact Brands With summer wrapping up, here’s a recap of other recent regulatory news: —Emergent BioSolutions smallpox vaccine ACAM2000 expanded its FDA approval to include mpox, which is from the same virus family as smallpox. During the mpox outbreak of 2022, the FDA permitted use of the vaccine under an expanded access investigational new drug application. The additional approval comes amid an ongoing mpox outbreak in Central Africa. —Three updated Covid-19 vaccines now have the FDA’s blessing for use during the upcoming respiratory infection season. The regulator approved and authorized updated Covid-19 vaccines from Moderna and partners BioNTech and Pfizer. The new shots address the KP.2 strain of the omicron variant of SARS-CoV-2. That’s close to the KP.3.1.1 subtype that is currently most prevalent in the U.S., according to the Centers for Disease Control and Prevention. The FDA previously told vaccine makers that shots addressing the KP.2 strain were preferred, if feasible, for the 2024-2025 vaccination season. Late last week, the FDA also authorized an updated version of a protein-based Covid-19 vaccine from Novavax. —Johnson & Johnson cancer drug lazertinib, brand name Lazcluze, is now FDA-approved as a first-line treatment for locally advanced or metastatic non-small cell lung cancer (NSCLC). The drug is a once-daily pill designed to target epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations, which must be detected by a companion diagnostic. For this indication, the approval specifies Lazcluze must be given in combination with Rybrevant, a J&J drug initially approved in 2021 as a treatment for NSCLC with exon 20 insertion mutations to EGFR. In March, the FDA approved Rybrevant as a first-line treatment for such cancers. —As expected, the FDA turned down Regeneron Pharmaceuticals’ application for linvoseltamab as a treatment for advanced cases of multiple myeloma. Regeneron forecast the rejection earlier this month during its conference call to discuss second quarter 2024 financial results, disclosing that that the FDA flagged unresolved findings with a third-party manufacturer of linvoseltamab, a bispecific antibody that targets the BCMA protein on multiple myeloma cells. Those findings concern another company’s drug candidate and Regeneron believes that matter has been resolved. However, another FDA inspection is required before the agency can approve the drug. —Regeneron did welcome a regulatory approval in Europe that marks the first for its bispecific antibody platform. The European Commission approved odronextamab, brand name Ordspono, as a treatment for follicular lymphoma or diffuse large B-cell lymphoma that has advanced after two or more earlier lines of therapy. The drug is designed to bind to CD20 on cancer cells and CD3 on T cells. Ongoing clinical trials are evaluating this drug as a monotherapy and in combinations as an earlier line of cancer treatment. —Liquidia received tentative FDA approval for Yutrepia as a treatment for pulmonary arterial hypertension (PAH). Yutrupeia is an inhalable powder formulation of treprostinil, a drug that United Therapeutics markets in injectable, oral, and inhaled formulations for the treatment of PAH. According to Liquidia, the FDA said Yutrepia met all benchmarks for quality, safety, and efficacy. However, final approval cannot be granted until the May 23, 2025, when United Therapeutics’ patent for its dry powder formulation of treprostinil expires. Liquidia is challenging the FDA’s decision. —The FDA lifted a partial clinical hold on an antibody drug conjugate (ADC) MediLink Therapeutics is developing in partnership with BioNTech. The partial hold on the drug, BNT326/YL202, was announced in mid-June after MediLink reported treatment-related adverse events. BioNTech said in addition to risk mitigation measures, the study will proceed with doses no higher than 3 mg per kilogram, where the safety profile was manageable and encouraging clinical activity was observed. BioNTech and MediLink began their partnership on the HER-3-targeting ADC last year. —Incyte already has a presence in graft-versus-host disease with Jakafi. FDA approval of axatilimab, brand name Niktimvo, gives the company another GVHD drug with a different approach. While Jakafi is a small molecule JAK inhibitor, Niktimvo is an antibody designed to block a protein called colony stimulating factor-1. FDA approval of the new drug covers the treatment chronic GVHD in adults after at least two prior lines of therapy. Niktimvo was initially developed by Syndax Pharmaceuticals. In 2021, Incyte and Syndax began a partnership on the drug; the two companies will share in commercialization of the therapy in the U.S. while Incyte will commercialize the product in the rests of the world. —The FDA approved Galderma’s nemolizumab, brand name Nemluvio, as a treatment for prurigo nodularis, a rare neuroimmune disease that leads to chronic itch and the formation of nodules on the skin. The antibody drug is designed to inhibit IL-31, a signaling protein associated with multiple inflammatory conditions. The drug is also under FDA review for atopic dermatitis; a regulatory decision is expected later this year. —AstraZeneca cancer drug Imfinzi expanded its approved lung cancer uses to include the treatment of adults with resectable early-stage non-small cell lung cancer (NSCLC). The latest approval covers use of the drug in combination with neoadjuvant chemotherapy before surgery and as an adjuvant monotherapy after surgery. The drug’s first lung cancer approval was in 2018 as a treatment for advanced cases NSCLC. In 2020, the FDA approved the drug for treating extensive-stage small cell lung cancer. —Ascendis Pharma won FDA approval for Yorvipath for hypoparathyroidism, a rare disease in which patients have low levels of parathyroid hormone. Approval of the drug, an engineered version of parathyroid hormone administered as a once-daily injection, comes as Takeda Pharmaceutical plans to discontinue production of Natpara, the only other engineered parathyroid hormone drug currently available. Ascendis plans to launch Yorvipath in the first quarter of next year. —The FDA rejected Lykos Therapeutics’ application seeking approval for midomafetamine (MDMA), a psychedelic drug the company had developed as a treatment for post-traumatic stress disorder (PTSD). According to San Jose-based Lykos, the FDA asked the company to conduct another Phase 3 clinical trial to further study the safety and efficacy of the drug, echoing concerns raised during an June advisory committee meeting. Lykos plans to request an FDA meeting to ask for a reconsideration of the regulatory decision and to discuss a potential resubmission of a new drug application. —Novartis drug iptcaopan, brand name Fabhalta, expanded its label with accelerated FDA approval in the rare kidney disease immunoglobulin A nephropathy. In this indication, the complement inhibitor will compete with Travere Therapeutics’ Filspari and Calliditas Therapeutics’ Tarpeyo. Fabhalta was first approved last December as a treatment for the rare blood disorder paroxysmal nocturnal hemoglobinuria. —The FDA delayed its regulatory decision for Humacyte’s engineered blood vessels. The agency told Humacyte it needs more time to complete its review of ATEV, the company’s bioengineered human tissue intended to serve as an alternative to harvesting a vein from a trauma patient. Durham, North Carolina-based Humacyte said it does not yet have a new target date for a regulatory decision. —Adaptimmune Therapeutics’ Tecelra became the first engineered cell therapy approved by the FDA as a treatment for a solid tumor. The accelerated approval covers the treatment of advanced cases of synovial sarcoma. Tecelra is made by engineering a patient’s T cells with a T cell receptor that recognizes a target on the inside of a cancer cell. —GSK cancer drug Jemperli broadened its label to cover the majority of endometrial cancer cases. The immunotherapy was initially approved in 2021 as a treatment for advanced or recurrent endometrial cancer that carries a particular genetic signature called a mismatch repair deficiency. The latest approval expands use of the drug to patients with mismatch repair proficient/microsatellite stable tumors. Such cases represent between 70% and 75% of endometrial cancer patients. Jemperli’s FDA approval in the expanded indication covers use of the therapy in combination with chemotherapy. Photo from Flickr user US Department of Education