germ cell cancers

BioNTech will pay $50 million and make a $200 million investment in Autolus Therapeutics as the company most famous for its COVID-19 vaccine boosts its cell therapy capabilities.Per deal terms, BioNTech will receive royalties on sales of Autolus obe-cel, a CAR-T therapy for leukemia that the Food and Drug Administration could approve by Nov. 16. The German biotech also has options to co-commercialize two earlier programs in the Autolus pipeline, dubbed AUTO1/22 and AUTO6NG, and gains access to a suite of technologies.Perhaps more importantly, the deal allows BioNTech to tap into Autolus manufacturing capacity, offering a cost-efficient set-up to speed development of its own BNT211 cell therapy for cancer, the company said Thursday. The CAR-T treatment is being evaluated for certain types of solid tumors, and BioNTech plans to begin a pivotal Phase 2 trial in second-line or later treatment of germ cell cancer this year.The two companies said the collaboration will help them both advance cell therapies to the market as Autolus takes advantage of the larger companys cash and BioNTech gains clinical and commercial supply infrastructure.As part of the deal, BioNTech will purchase $200 million of Autolus American Depositary Shares in a private placement. The investment will give BioNTech the right to appoint a director on Autolus board.Autolus also announced an offering of more than 58 million American Depositary Shares at $6 each, raising $350 million.The financial influx will help Autolus fund operations for longer. Previously, the company had estimated its cash holdings would be enough to keep the lights on into 2025.Meanwhile, BioNTech, with plenty of cash on hand from the success of its COVID-19 vaccine developed with Pfizer, has the room to bet on smaller biotechs. Last year, the company moved into antibody-drug conjugates via a licensing deal with Chinas Duality Biologics. The company also bought rights to a new cancer drug from privately held OncoC4. '

At the European Society for Medical Oncology, BioNTech detailed signs of clinical activity with BNT211 and a persistence of CAR-T cells when combined with CARVac. MADRID—BioNTech’s new manufacturing process for CAR-T seems to have done the trick in boosting the potency of the solid tumor therapy BNT211, but that bit of extra juice appears to have upped the side effect profile as well. The famed mRNA company has some dosing changes in mind that could help bring down the rates of cytokine release syndrome (CRS) seen in an ongoing early-stage trial. And according to Benjamin Rengstl, director of clinical development and immunoreceptor therapy, the data shows that CAR-T can indeed work in solid tumors. At the European Society for Medical Oncology Congress, BioNTech detailed signs of clinical activity with BNT211 and a persistence of CAR-T cells when combined with CARVac, the biotech’s RNA vaccine that’s designed to boost efficacy of the CAR-T cells. BNT211 targets the antigen Claudin-6 (CLDN6), which occurs in many solid tumors including ovarian cancer, sarcoma, testicular cancer, endometrial cancer and gastric cancer. The trial tested four dose levels with BNT211 alone or with CARVac. An overall response rate of 45% was seen in 38 of the 44 evaluable patients, plus a disease control rate of 74%. “Now finally, we can answer the question that we really do see a difference … in the [pharmacokinetics] of the CAR-T cells, so they persist way longer,” Rengstl told Fierce Biotech on the sidelines of the conference in Madrid. “I have to say the new product is really more potent but also a bit more toxic.” Of 27 patients who received dose level two with or without CARVac, 13 experienced partial responses with an ORR of 59% and a disease control rate of 95%. These patients also showed a prolonged persistence of the CAR-T cells. “So this means that basically every patient is benefiting. There was a single patient out of … 24 not responding to the treatment,” Rengstl said. BioNTech changed the manufacturing process after providing a peak at BNT211 during last year’s ESMO Congress. The new data cut features a more automated manufacturing process that is more robust, scalable and creates a more potent product. BioNTech then conducted a new dose escalation process, presenting a very early look at the American Society for Clinical Oncology meeting in June. At ESMO, more follow-up data is available to begin to fill in the efficacy and safety picture. Of the 44 total patients, there were 23 cases of CRS, a known complication of CAR-T therapy where the immune system overreacts to a drug and causes fever, nausea and other symptoms that can become serious. BioNTech said these adverse events were “dose-dependent.” Most of the events were grades 1 and 2, representing less serious cases, but there was one grade 3 and a grade 4. The patient with the grade 4 CRS case experienced acute respiratory distress syndrome and spent “quite a while” in intensive care but has since recovered. Rengstl said the person remains on treatment and is still benefiting about a half year later. This person was the only patient to receive the highest dose allowed under the trial protocol, which BioNTech has since backed off from. BioNTech is zeroing in on the second dose level, which is showing efficacy without the safety challenges. Rengstl believes the toxicities can be managed at this level. “The issue is that basically we are pioneering in the field of solid tumors. So there's not much data out there. All that we know about classic CAR-T cells is coming from [hematology] indications and you cannot really translate this,” Rengstl said. One positive sign in the safety data is that there were low levels of neurotoxicity with just mild cases reported, he pointed out. There were, however, liver toxicities that did not occur with BioNTech’s previous product that was created using the previous manufacturing process. Rengstl said this is likely because the new process creates more cytokines, which are activating the endogenous immune system and organs like the liver. “We are still in the phase of figuring out what is going on there, but we are confident that with certain measures we can mitigate those side effects,” he said. BioNTech still doesn’t know about the durability of BNT211. That’s something the company will need to prove to make a real change on the CAR-T scene, where relapse has been common. It’s a known issue that patients typically relapse on CAR-T after a certain point, but Rengstl believes the early data that include CARVac show some promise on this issue. “We also have treated patients with redosing and could show that they can respond again, so we are quite confident that we will see it, finally, not only on the PK level, the contribution of the vaccine,” he said. Another challenge for the BNT211 program is simply being first. Rengstl said BioNTech is working with European regulators now to negotiate a single-arm trial for future studies instead of a randomized one as requested. There's just too much risk for patients with germline tumors, who are all typically very young with testicular cancer, he said.  "We are, at the moment, pushing back a bit," Rengstl said. "The comparator that authorities might want to have is palliative care. So for me this makes no sense to compare a potential curative approach with one that prolongs life—not really, because they have a median survival of three to four months." BioNTech will need to sort out the safety and regulatory issues, but the company has put up efficacy to show that CAR-T could have a future beyond blood cancers. The next steps are to start the phase 2 portion of the trial, which will focus on germ cell cancers, in the EU and U.S., where Rengstl says there are still discussions going on.  "The EMA is the authority that we are talking most with and now with the data that we're presenting later today, there is more to discuss, more indications and more trials," he said. Rengstl said that patients have reported an improved quality of life compared to previous chemotherapy: “So often we get the information that patients didn't come to the visit, but sent greetings from vacation.”  To read more of Fierce Biotech's coverage of the ESMO Congress, click here. Fierce Pharma's coverage is available here.

Pedmarqsi™ is the First and Only Approved Therapy in the European Union for Reducing the Risk of Cisplatin-induced Hearing Loss (Ototoxicity) in Pediatric Patients with Localized, Non-metastatic Solid Tumors RESEARCH TRIANGLE PARK, N.C., June 06, 2023 (GLOBE NEWSWIRE) -- Fennec Pharmaceuticals Inc. (NASDAQ: FENC; TSX: FRX), a commercial stage specialty pharmaceutical company, today announced Pedmarqsi™– known as PEDMARK® in the U.S. – was granted marketing authorization by the European Commission. Pedmarqsi is the first and only approved therapy in the EU for the prevention of ototoxicity (hearing loss) induced by cisplatin chemotherapy in patients 1 month to <18 years of age with localised, non-metastatic, solid tumors. Further, Pedmarqsi was granted the marketing authorization under the paediatric-use marketing authorization (PUMA) which includes 8 years plus 2 years of data and market protection. “Today's approval by the European Commission for Pedmarqsi to help reduce the risk of hearing loss is critical for the approximately four thousand children treated with cisplatin for solid tumors that have not spread,” said Rosty Raykov, chief executive officer of Fennec Pharmaceuticals. “Fennec is proud to bring this safe and effective therapy to the marketplace to mitigate the risk of permanent and irreversible bilateral hearing loss which occurs in approximately 60 percent of children treated with cisplatin and can be as high as 90 percent.1 We look forward to making this important treatment available to the pediatric oncology community in the EU as soon as possible.” The European Commission granted marketing authorization approval to Pedmarqsi following the adoption of a positive opinion by the Committee for Medicinal Products for Human Use (CHMP) earlier this year. The CHMP’s decision was based on safety and efficacy data from two pivotal open-label, randomized Phase 3 trials (SIOPEL 6 and Clinical Oncology Group [COG] Protocol ACCL0431), which compared Pedmarqsi plus cisplatin-based regimen to cisplatin-based regimens alone for the reduction of cisplatin-induced hearing loss in pediatric patients. The marketing authorization is applicable to all 27 European Union member states, as well as Iceland, Norway and Liechtenstein. PEDMARK® was approved by the U.S. Food and Drug Administration (FDA) in September 2022. About Cisplatin-Induced Ototoxicity Cisplatin and other platinum compounds are essential chemotherapeutic agents for the treatment of many pediatric malignancies. Unfortunately, platinum-based therapies can cause ototoxicity, or hearing loss, which is permanent, irreversible, and particularly harmful to the survivors of pediatric cancer.2 The incidence of ototoxicity depends upon the dose and duration of chemotherapy, and many of these children require lifelong hearing aids or cochlear implants, which can be helpful for some, but do not reverse the hearing loss and can be costly over time.3 Infants and young children that are affected by ototoxicity at critical stages of development lack speech and language development and literacy, and older children and adolescents often lack social-emotional development and educational achievement.4 PEDMARK® (sodium thiosulfate) PEDMARK® is the first and only U.S. Food and Drug Administration (FDA) approved therapy indicated to reduce the risk of ototoxicity associated with cisplatin treatment in pediatric patients with localized, non-metastatic, solid tumors. It is a unique formulation of sodium thiosulfate in single-dose, ready-to-use vials for intravenous use in pediatric patients. PEDMARK is also the only therapeutic agent with proven efficacy and safety data with an established dosing paradigm, across two open-label, randomized Phase 3 clinical studies, the Clinical Oncology Group (COG) Protocol ACCL0431 and SIOPEL 6. In the U.S. and Europe, it is estimated that, annually, more than 10,000 children may receive platinum-based chemotherapy. The incidence of ototoxicity depends upon the dose and duration of chemotherapy, and many of these children require lifelong hearing aids. There is currently no established preventive agent for this hearing loss and only expensive, technically difficult, and sub-optimal cochlear (inner ear) implants have been shown to provide some benefit. Infants and young children that suffer ototoxicity at critical stages of development lack speech language development and literacy, and older children and adolescents lack social-emotional development and educational achievement. PEDMARK has been studied by co-operative groups in two Phase 3 clinical studies of survival and reduction of ototoxicity, COG ACCL0431 and SIOPEL 6. Both studies have been completed. The COG ACCL0431 protocol enrolled childhood cancers typically treated with intensive cisplatin therapy for localized and disseminated disease, including newly diagnosed hepatoblastoma, germ cell tumor, osteosarcoma, neuroblastoma, medulloblastoma, and other solid tumors. SIOPEL 6 enrolled only hepatoblastoma patients with localized tumors. Indications and Usage PEDMARK® (sodium thiosulfate injection) is indicated to reduce the risk of ototoxicity associated with cisplatin in pediatric patients 1 month of age and older with localized, non-metastatic solid tumors. Limitations of Use The safety and efficacy of PEDMARK have not been established when administered following cisplatin infusions longer than 6 hours. PEDMARK may not reduce the risk of ototoxicity when administered following longer cisplatin infusions, because irreversible ototoxicity may have already occurred. Important Safety Information PEDMARK is contraindicated in patients with history of a severe hypersensitivity to sodium thiosulfate or any of its components. Hypersensitivity reactions occurred in 8% to 13% of patients in clinical trials. Monitor patients for hypersensitivity reactions. Immediately discontinue PEDMARK and institute appropriate care if a hypersensitivity reaction occurs. Administer antihistamines or glucocorticoids (if appropriate) before each subsequent administration of PEDMARK. PEDMARK may contain sodium sulfite; patients with sulfite sensitivity may have hypersensitivity reactions, including anaphylactic symptoms and life-threatening or severe asthma episodes. Sulfite sensitivity is seen more frequently in people with asthma. PEDMARK is not indicated for use in pediatric patients less than 1 month of age due to the increased risk of hypernatremia or in pediatric patients with metastatic cancers. Hypernatremia occurred in 12% to 26% of patients in clinical trials, including a single Grade 3 case. Hypokalemia occurred in 15% to 27% of patients in clinical trials, with Grade 3 or 4 occurring in 9% to 27% of patients. Monitor serum sodium and potassium levels at baseline and as clinically indicated. Withhold PEDMARK in patients with baseline serum sodium greater than 145 mmol/L. Monitor for signs and symptoms of hypernatremia and hypokalemia more closely if the glomerular filtration rate (GFR) falls below 60 mL/min/1.73m2. Administer antiemetics prior to each PEDMARK administration. Provide additional antiemetics and supportive care as appropriate. The most common adverse reactions (≥25% with difference between arms of >5% compared to cisplatin alone) in SIOPEL 6 were vomiting, nausea, decreased hemoglobin, and hypernatremia. The most common adverse reaction (≥25% with difference between arms of >5% compared to cisplatin alone) in COG ACCL0431 was hypokalemia. Please see full Prescribing Information for PEDMARK® at: . About Fennec Pharmaceuticals Fennec Pharmaceuticals Inc. is a specialty pharmaceutical company focused on the development and commercialization of PEDMARK® and Pedmarqsi to reduce the risk of platinum-induced ototoxicity in pediatric patients. Further, PEDMARK received FDA approval in September 2022 and European Commission Marketing Authorization in June 2023 for Pedmarqsi. PEDMARK has received Orphan Drug Exclusivity in the U.S. for seven years of market protection and Pedmarqsi has received Pediatric Use Marketing Authorization in Europe which includes eight years plus two years of data and market protection. Fennec has a license agreement with Oregon Health and Science University (OHSU) for exclusive worldwide license rights to intellectual property directed to sodium thiosulfate and its use for chemoprotection, including the reduction of risk of ototoxicity induced by platinum chemotherapy, in humans. For more information, please visit . Forward Looking Statements Except for historical information described in this press release, all other statements are forward-looking. Words such as “believe,” “anticipate,” “plan,” “expect,” “estimate,” “intend,” “may,” “will,” or the negative of those terms, and similar expressions, are intended to identify forward-looking statements. These forward-looking statements include statements about our business strategy, timeline and other goals, plans and prospects, including our commercialization plans respecting PEDMARK® and Pedmarqsi, the market opportunity for and market impact of PEDMARK® and Pedmarqsi, its potential impact on patients and anticipated benefits associated with its use, and potential access to further funding after the date of this release. Forward-looking statements are subject to certain risks and uncertainties inherent in the Company’s business that could cause actual results to vary, including the risks and uncertainties that regulatory and guideline developments may change, scientific data and/or manufacturing capabilities may not be sufficient to meet regulatory standards or receipt of required regulatory clearances or approvals, clinical results may not be replicated in actual patient settings, unforeseen global instability, including political instability, or instability from an outbreak of pandemic or contagious disease, such as the novel coronavirus (COVID-19), or surrounding the duration and severity of an outbreak, protection offered by the Company’s patents and patent applications may be challenged, invalidated or circumvented by its competitors, the available market for the Company’s products will not be as large as expected, the Company’s products will not be able to penetrate one or more targeted markets, revenues will not be sufficient to fund further development and clinical studies, our ability to obtain necessary capital when needed on acceptable terms or at all, the Company may not meet its future capital requirements in different countries and municipalities, and other risks detailed from time to time in the Company’s filings with the Securities and Exchange Commission including its Annual Report on Form 10-K for the year ended December 31, 2022. Fennec disclaims any obligation to update these forward-looking statements except as required by law. For a more detailed discussion of related risk factors, please refer to our public filings available at and . PEDMARK® and Fennec® are registered trademarks of Fennec Pharmaceuticals Inc. ©2023 Fennec Pharmaceuticals Inc. All rights reserved. FEN-1503-v1 Investors: Robert Andrade Chief Financial Officer Fennec Pharmaceuticals Inc. +1 919-246-5299 Corporate and Media: Lindsay Rocco Elixir Health Public Relations +1 862-596-1304 lrocco@elixirhealthpr.com 1 Langer T, Zehnhoff-Dinnesen A, Radtke S, et al. Understanding Platinum-Induced Ototoxicity. Trends in Pharmacological Sciences. August 2013, Vol. 34, No. 8:458-469. 2 Rybak L. Mechanisms of Cisplatin Ototoxicity and Progress in Otoprotection. Current Opinion in Otolaryngology & Head and Neck Surgery. 2007, Vol. 15: 364-369. 3 Landier W. Ototoxicity and Cancer Therapy. Cancer. June 2016 Vol. 122, No.11: 1647-1658. 4 Bass JK, Knight KR, Yock TI, et al. Evaluation and Management of Hearing Loss in Survivors of Childhood and Adolescent Cancers: A Report from the Children's Oncology Group. Pediatric Blood & Cancer. 2016 Jul;63(7):1152-1162.