On June 28, 2021 CEL-SCI Corporation (NYSE American: CVM) reported results from its 9.5 year pivotal Phase 3 study for its immunotherapy Multikine (Leukocyte Interleukin, Injection)* in the treatment of advanced (stages III and IV) primary (previously untreated) squamous cell carcinoma of the head and neck (SCCHN) (Press release, Cel-Sci, JUN 28, 2021, View Source [SID1234584422]).

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In the intent to treat (ITT) advanced primary SCCHN patients the study showed a statistically significant (p=0.0236, HR=0.68) overall survival benefit of 14.1% with overall survival (OS) of 62.7% at 5 years for the group of patients receiving the Multikine treatment regimen followed by surgery and radiotherapy therapy, but not chemotherapy, as part of their standard of care (SOC) treatment. The OS benefit increased over time. This group represents about 155,000 patients worldwide, or about 40% of all advanced primary head and neck cancer cases annually. Patients treated with the same Multikine treatment regimen prior to surgery and radiotherapy, but who also received chemotherapy, did not exhibit this survival advantage. The chemotherapy, cisplatin, was given intravenously and may have negated the survival benefit imparted by Multikine immunotherapy in these patients.

This global trial enrolled 928 stage III and IVa patients through 78 sites on 3 continents. The ITT population comprised of 923 patients, as 5 randomized patients were never treated. The two main comparator arms of the study were: the Multikine treatment regimen (Multikine plus CIZ: cyclophosphamide; indomethacin; zinc-multivitamins) plus SOC vs. SOC alone. In each of these comparator arms, patients were determined by pathology following surgery to receive radiotherapy only or concurrent radio-chemotherapy. These treatments were prescribed by the protocol and are based on the NCCN (National Comprehensive Cancer Network) Guidelines for the treatment of SCCHN patients. The data were analyzed per the protocol and the Statistical Analysis Plan.

Results for the patients who did not receive chemotherapy treatment as part of their SOC are listed below. This is the group for which CEL-SCI plans to seek FDA approval:

1) Patients treated with the Multikine treatment regimen plus SOC vs. SOC alone had an overall survival benefit of 14.1% at 5 years which exceeded the pre-defined 10% overall survival benefit set out for the study population as a whole. This result was statistically significant (ITT; p =0.0236, HR=0.68) with a robust and durable duration effect exceeding 5 years.

2) The corresponding overall survival at 3 years and 5 years for each study treatment group was as follows: Multikine treatment regimen (Multikine plus CIZ: cyclophosphamide; indomethacin, zinc-multivitamins) plus SOC was 72.4% at 3 years, 62.7% at 5 years; Multikine (no CIZ) plus SOC was 78.8% at 3 years, 55.5% at 5 years. SOC alone was 67.5% at 3 years, 48.6% at 5 years. The primary survival comparison was pre-defined only between the first and last groups.

3) The OS advantage increased over time and was evident from the inception of the study participation for this group of patients through the end of the follow up period with a median follow up time greater than 7 years for those still alive.

4) No safety issues for Multikine were found during or as a result of its administration, including no late effects, in the overall treated patient population.

When the complete study population to which the Multikine treatment regimen was administered (i.e., the combined lower risk (no chemotherapy) and higher risk (with chemotherapy added)) was compared to control, the study did not achieve its primary endpoint of a 10% improvement in overall survival. However, the OS benefit of 14.1% at 5 years for the lower risk subgroup (no chemotherapy) exceeded the 10% OS benefit set out for the study population as a whole. In addition, as the OS results for the lower risk of recurrence patients (no chemotherapy) are significant (two-sided p=0.0236, HR=0.68) and the effect is robust, durable and increasing over time, CEL-SCI plans to seek FDA approval for Multikine cancer immunotherapy in this underserved patient population. This indication represents a dire unmet medical need with the last FDA approval being many decades ago. CEL-SCI has Orphan Drug designation from the FDA for the neoadjuvant therapy in patients with squamous cell carcinoma of the head and neck – the patient population treated in this Phase 3 study.

The analysis of this separate group is expected to meet regulatory requirements for FDA submission based on the protocol and Statistical Analysis Plan, which were prospectively concluded before database lock and unblinding.

Geert Kersten, Chief Executive Officer of CEL-SCI remarked, "Multikine demonstrated a significant survival benefit in the group whose standard of care did not include chemotherapy and a favorable safety profile across the entire patient population. Based on this landmark study data, we intend to seek FDA approval for what could become the first treatment in newly diagnosed advanced primary head and neck cancer in many decades. If approved, Multikine would address the needs of approximately 155,000 patients diagnosed annually worldwide who are currently slated for surgery plus radiotherapy and would significantly increase their chances of overall survival. Our aim with Multikine was to develop a treatment that will extend survival, and clearly this has been achieved in this patient population. In addition, we wanted to develop a treatment that does not add toxicity and does not make other cancer treatments more difficult to bear. We appear to have achieved this goal as well. We are grateful to all the patients and their families who volunteered to participate in the world’s largest and most rigorous Phase 3 study in advanced primary head and neck cancer. We are confident that the robust overall survival benefit shown in this pivotal study along with the safety profile of Multikine clearly demonstrates the benefit of neoadjuvant immunotherapy in this patient population and may lead to a new way to treat advanced primary head and neck cancer."

Dr. Eyal Talor, Chief Scientific Officer of CEL-SCI and the developer of Multikine commented, "These data, combined with what we know of Multikine’s mechanism of action, demonstrate Multikine’s potential to impart long term overall survival advantage and a beneficial effect on the anti-tumor immune response in patients who have not been treated with chemotherapy (cisplatin) which is known to be highly toxic. In patients not indicated to receive chemotherapy as part of their standard of care, treatment with Multikine neoadjuvant regimen demonstrated a statistically significant, robust and durable overall survival benefit. The data possibly indicate that the Multikine treatment regimen is capable of altering the course of disease in this population. Perhaps most impressive in the Multikine treated group not receiving chemotherapy was the fact that the overall survival benefit imparted by Multikine increased over time as compared to overall survival in control, suggesting that the Multikine immunotherapy neoadjuvant treatment stands to add great benefit to the intent to cure – current standard of care."

About Multikine

Multikine (Leukocyte Interleukin, Injection) is an investigational cancer immunotherapy that is known to contain 14 natural human cytokines, the body’s immune system regulators including interleukins, interferons, chemokines, and colony stimulating factors which are elements of the body’s natural mix of defenses against cancer and other diseases. A patented, mass-produced, off the shelf and ready to use non-autologous biological product, Multikine is manufactured using a proprietary process following Good Manufacturing Practice (GMP) requirements from Source Leukocytes, an FDA licensed product, at CEL-SCI’s manufacturing facility near Baltimore, Maryland.

About Head and Neck Cancer

Approximately 650,000 new cases of head and neck cancer are diagnosed each year globally, of which approximately 60,000 are in the U.S. and 105,000 in Europe. Head and neck cancer represents 6% of all cancers and leads to 300,000 deaths annually. Advanced (stages III and IV) primary (previously untreated) squamous cell carcinoma of the head and neck represent approximately 386,000 cases per year and about 40% of these, or approximately 155,000, are patients diagnosed at lower risk for recurrence and therefore are given only radiotherapy following surgery as part of their standard of care, and no chemotherapy.

On June 28, 2021 Tempest Therapeutics, Inc. (Nasdaq: TPST) ("Tempest"), a clinical-stage oncology company developing potentially first-in-class therapeutics that combine both targeted and immune-mediated mechanisms, reported the closing of its merger with Millendo Therapeutics, Inc. ("Millendo") (Press release, Tempest Therapeutics, JUN 28, 2021, View Source [SID1234585166]). Tempest’s stock will commence trading on June 28, 2021 on the Nasdaq Global Select Market under the trading symbol "TPST."

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In support of the merger, Tempest secured investments from a premier syndicate of healthcare investors composed of Versant Ventures, Rock Springs Capital, F-Prime Capital, Monashee Investment Management, Quan Capital, Lyfe Capital, Maven Investment Partners US, Lilly Asia Ventures and Eight Roads Ventures for a $30 million PIPE financing that closed concurrent with the completion of the merger. The net proceeds of the transaction are expected to fund the company’s operations and advancement of its programs into early 2023, including:

TPST-1495 (dual EP2/4 antagonist): completion of the ongoing monotherapy Phase 1 dose finding study, opening of a combination dose finding study of TPST-1495 with pembrolizumab, and the planned opening of both monotherapy and combination expansion studies in targeted patient populations;
TPST-1120 (PPAR⍺ antagonist): completion of the ongoing Phase 1 study of TPST-1120 in combination with nivolumab, and the expected initiation and completion of enrollment of a global, randomized Phase 1b/2 study of TPST-1120 in combination with the standard-of-care first-line regimen of atezolizumab and bevacizumab in previously-untreated patients with advanced or metastatic HCC, pursuant to a collaboration between Tempest and F. Hoffmann-La Roche; and
Research: advancement of additional novel oncology research programs, including an oral inhibitor of TREX-1 intended to selectively activate STING in tumors and stimulate anti-tumor immunity.
"The closing of this merger fulfills an important 2021 goal for Tempest," said Steve Brady, chief executive officer of Tempest. "With our novel programs, including TPST-1495 and TPST-1120 progressing in the clinic, access to the public markets was of strategic importance as we look forward to a number of potential catalysts in the future and advance towards our goal to offer patients with cancer meaningful therapeutic options."

Transaction Terms and Leadership Team Updates

In connection with the closing of the merger, Millendo effected a 1:15 reverse split of its common stock. Tempest has approximately 6.7 million shares of common stock outstanding after giving effect to the terms of the transaction. Tempest stockholders prior to the merger, combined with investors in the concurrent financing, collectively own approximately 81% of the outstanding shares, and prior Millendo stockholders own approximately 19% of the outstanding shares.

Effective as of the closing of the merger, Geoff Nichol, chief medical officer of BioMarin, and Steve Brady, chief executive officer of Tempest, are joining Mike Raab, president and chief executive officer of Ardelyx, Tom Woiwode, managing director, Versant Ventures, Tom Dubensky, president of Tempest, and Stella Xu, managing director, Quan Capital, on the Tempest board of directors.

Piper Sandler served as the exclusive financial advisor and placement agent to Tempest, and Sidley Austin served as Tempest’s legal counsel. SVB Leerink served as the exclusive financial advisor to Millendo and WilmerHale served as Millendo’s legal counsel.

On June 28, 2021 Sanofi’s ongoing efforts to reduce the complexity of its Consumer Healthcare portfolio and accelerate its growth trajectory, reported that it has signed an agreement with STADA for the divestiture of 16 Consumer Healthcare products commercialized in Europe (Press release, Sanofi, JUN 28, 2021, View Source [SID1234584391]). The transaction with STADA ensures that these products will continue to be available to consumers.

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"As discussed during our Capital Markets Day in February, simplifying the CHC product portfolio is an important part of our strategy to focus our resources and efforts where we can bring the most value, especially to consumers. We are pleased these products will continue to be available for consumers as we focus on becoming a fully integrated standalone business" said Julie Van Ongevalle, Executive Vice-President, Sanofi and Head of Sanofi Consumer Healthcare.

The agreement covers the registrations, trademarks, and related commercial rights of 16 products across Europe.

"This acquisition further strengthens STADA as a top-five player in Europe’s consumer healthcare market, supports our growth acceleration, and is another proof point of STADA as a go-to-partner," commented STADA’s CEO, Peter Goldschmidt.

Sanofi does not anticipate any impact of this divestiture to its European-based workforce.

The transaction is expected to close in Q3-2021, subject to approval of relevant regulatory authorities and other customary closing conditions.

On June 28, 2021 SHINE Medical Technologies LLC reported that it has closed a $150-million Series C-5 financing (Press release, Shine Medical Technologies, JUN 28, 2021, View Source;pk_kwd=shine-medical-technologies-closes-150-million-series-c-5-financing [SID1234584407]). Koch Disruptive Technologies (KDT) led the round, which also included participation by Fidelity Management & Research Company, Baillie Gifford and other new and current investors . The financing will support SHINE’s commercialization of its diagnostic and therapeutic medical isotope technologies and position the company for future growth as it works toward developing new fusion-based technology applications.

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"KDT is an incredible strategic partner for SHINE as we commercialize both diagnostic and therapeutic medical isotopes, and work towards fusion-based nuclear waste recycling and clean energy production," said Greg Piefer, Chairman and CEO of SHINE. "Koch knows how to scale a company, with more than 120,000 employees around the world, and we look forward to tapping that knowledge as we continue to grow. SHINE’s mission is to usher in a new era of nuclear fusion technology and Koch, which is among the biggest players in energy, is a great long-term, strategic match for us as we pursue our ultimate goal: fusion-based clean energy. We are grateful for their confidence and investment in SHINE."

"SHINE’s innovative medical isotope technologies, which play a crucial role in identifying and treating patients with debilitating diseases, are astounding," said Chase Koch, President of KDT. "We believe SHINE has the potential to change not only the production and supply of medical isotopes, but to transform industrial segments globally by leveraging the company’s nuclear-fusion based technology for industrial inspection and imaging, nuclear waste recycling and energy production. Koch’s global knowledge networks and capabilities are uniquely suited to help SHINE’s impressive team implement its vision to advance fusion technology. We look forward to a productive partnership."

An existing SHINE facility produces the therapeutic medical isotope lutetitum-177 (Lu-177). Radiotherapeutics are one of the fastest growing areas of oncology and has significant potential for the treatment of several cancers because of their ability to directly irradiate cancer including at the late stages. SHINE’s manufacturing process can produce high-specific-activity Lu-177, the form of the isotope most in demand by today’s clinical trial sponsors. Last December, SHINE also broke ground for a large-scale therapeutic isotope plant, which is expected to be operational in mid-2022 and will produce Lu-177.

SHINE is also constructing a U.S. fusion-based medical isotope production facility in Janesville, Wisconsin, to produce molybdenum-99 (Mo-99), which more than 40 million patient procedures rely on each year. There has been little production of Mo-99 in the United States for decades – contributing to chronic shortages of the isotope – and this production facility will be capable of supplying more than one-third of the global demand for Mo-99. SHINE announced in May a location for its new European medical isotope production facility, which when combined with the capacity of SHINE’s U.S. plant will give the company the ability to produce 70 percent of the global patient need for Mo-99. The production facility will be driven by nuclear fusion technology that does not require a reactor and is cleaner, safer and more sustainable than a nuclear research reactor.

"SHINE is grateful for the confidence of our world-class investor syndicate and the ongoing support of our early-stage investors," said Todd Asmuth, SHINE’s President and Chief Strategy Officer. "The support of our institutional and individual investors and local, state and federal partners ensures that SHINE can fully execute its medical isotope plans by building multiple facilities and improving the lives of people around the world. As we bring these production facilities online, we will move into nuclear waste recycling and clean energy production, the next two phases of our plan. By doing so, we will continue to build long-term value for our stakeholders, including our customers, physicians and their patients, our employees and our shareholders."

On June 28, 2021 Eikonoklastes Therapeutics, a preclinical stage biopharmaceutical company, reported the closing of a Series A financing round, less than a year after the company emerged from stealth with its seed financing (Press release, Eikonoklastes Therapeutics, JUN 28, 2021, View Source [SID1234584423]).

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Eikonoklastes is developing next-generation tissue factor (TF) immunotherapies to treat a broad range of cancers beginning with Triple Negative Breast Cancer (TNBC), an aggressive and often lethal form of breast cancer that comprises 15% of all breast cancers. The therapies also have the potential to address several other non-cancer diseases with significant unmet clinical need. The company has engineered molecules which attack three key components of the tumor microenvironment (the tumor cells, the diseased neovasculature, and tumor stem cells) by activating the body’s natural immune system and is therefore efficacious without harming normal cells.

The most recent round of funding, led by CincyTech with participation from New York-based Elk Capital Ventures and others, will support Investigational New Drug (IND) enabling studies for Eikonoklastes Therapeutics’ L-ICON3 immune conjugate platform. Details of the financing were not disclosed, but Eikonoklastes Chief Executive Officer, Bruce Halpryn, Ph.D., said the initial target was significantly oversubscribed.

Halpryn said the new investor syndicate will help Eikonoklastes meet its objective of treating one of the most deadly cancers in medicine and establish a foundation for future growth. "We are thrilled to welcome Elk Capital and Jobs Ohio to our strong base of investors, as we seek to develop innovative medicines to treat patients with cancer and other severe diseases with substantial unmet clinical need," Halpryn said.

"We have made tremendous progress and have even bigger plans ahead of us," said Sam Lee, MD/MBA co-founder and Chief Business Officer. "We will continue strategically allocating capital to efficiently develop L-ICON3 toward the clinic and expand our platform capabilities."

"The Eikonoklastes management team has an impressive track record of building significant value," said Tom Finn, independent board member of Eikonoklastes and retired president of Procter & Gamble Global Personal Health Care. "The Series A financing positions the company to continue forging ahead towards bringing much needed new medicines to patients."

Jobs Ohio, Rev1, and other undisclosed investors also participated in the Series A financing.