On December 14, 2023 Sonnet BioTherapeutics Holdings, Inc. (NASDAQ:SONN) ("Sonnet" or the "Company"), a biopharmaceutical company developing innovative targeted biologic drugs focused on oncology, reported its financial results for the fiscal year ended September 30th, 2023 and provided a business update (Press release, Sonnet BioTherapeutics, DEC 14, 2023, View Source [SID1234638577]).

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"Sonnet has had a very productive year, exemplified by important achievements across our pipeline. The successful completion of the Phase 1 SB102 study with SON-1010 in healthy volunteers, combined with the initial data reported from the Phase 1 SB101 study in cancer patients propelled us forward into receiving FDA Investigational New Drug (IND) acceptance for the Phase 1b/2a SB221 combination study of SON-1010 with Roche’s atezolizumab, in platinum-resistant ovarian cancer (PROC)," commented Pankaj Mohan, Ph.D., Founder and CEO. "Our efforts to advance our pipeline continue and are accompanied by Janssen’s ongoing evaluation of SON-1010, SON-1210 and SON-1410 in combination with certain proprietary cell therapy assets. We are also working diligently to complete enrollment of the first portion of the Phase 1b SB211 study of SON-080 in chemotherapy-induced peripheral neuropathy (CIPN), with the hope of having early safety data available during the first quarter of 2024. We also expect to be able to share safety data from the SB102 and SB221 studies of SON-1010 during the first half of the year. In all, 2024 should be another exciting year for the company."

Fiscal Year 2023 and Recent Corporate Updates

Announced Collaboration Agreement with Roche: On January 9, 2023, Sonnet announced a collaboration agreement with Roche for the clinical evaluation of SON-1010 with atezolizumab. The companies have entered into a Master Clinical Trial and Supply Agreement (MCSA), along with ancillary Quality and Safety Agreements, to study the safety and efficacy of the combination of SON-1010 and atezolizumab in a platinum-resistant ovarian cancer (PROC) patient setting. Further, the companies will provide SON-1010 and atezolizumab, respectively, for use in the Phase 1b/Phase 2a combination safety, dose-escalation, and efficacy study (SB221). On August 16, Sonnet announced that the FDA accepted the Investigational New Drug application (IND) for the use of SON-1010 in ovarian cancer, authorizing the companies to move forward with the SB221 trial.

Sonnet is pleased to provide the following updates on its pipeline assets

SON-1010 (IL12-FHAB): In January 2023, Sonnet announced data from SB102, a single-ascending dose (SAD) Phase 1 clinical trial designed to carefully study the pharmacokinetics (PK) and pharmacodynamics (PD) of SON-1010 in preparation for combination studies. Typical dose-related increases were seen with SON-1010 in the serum after subcutaneous (SC) administration. Drug levels peaked at about 11 hours and the mean elimination half-life (t½) after the 150 ng/kg dose of SON-1010 was 112 hours, compared to 12 hours for rhIL-12 given SC, as reported in the literature.

In April, Sonnet presented additional data from the SB101 study of SON-1010 at the 2023 AACR (Free AACR Whitepaper) Annual Meeting. SB101 is a SAD trial in adult patients with advanced solid tumors that commenced in the second quarter of 2022 and is currently enrolling the final dose cohort. Of the 15 patients from SB101 who were evaluable for follow-up at this latest cutoff, 9 had stable disease at the first follow-up scan, 4 of which were already progressing at study entry. At the four-month follow-up, 5 of 14 patients remained stable at the second scan, suggesting clinical benefit of SON-1010 in 36% of patients. As an example, the first patient dosed, who has an aggressive endometrial sarcoma, had target tumor shrinkage with complete resolution of ascites at one point and has been clinically stable for over a year. SON-1010 has been safe and tolerable at all doses tested to date. Adverse events have generally been mild/moderate and transient in nature, with no study discontinuations for safety reasons. In addition, adverse effects have been less numerous and less intense with subsequent doses. Comparison of the PK curves between the two studies suggests that SON-1010 may be targeting tumors, as it was designed to do. Cytokine analysis following each dose revealed controlled and prolonged induction of interferon gamma (IFNγ) that peaked at 24 to 48 hours and returned to baseline after 2 to 4 weeks, which may improve tumor control. A small increase in IL-10 was observed with each dose, as might be expected in response to IFNγ. There was either a minimal or no signal for IL-1β, IL-6, IL-8, and TNFα and no indication of any potential for cytokine release syndrome (CRS) at these doses. Safety data from final dose escalation in the SB101 study are expected during the first half of 2024.

Following FDA acceptance of the IND in August, Sonnet launched the SB221 study with several patients currently being dosed. This trial consists of a modified 3+3 dose-escalation design in Part 1 to establish the maximum tolerated dose (MTD) of SON-1010 with a fixed dose of atezolizumab. Clinical benefit in PROC will be confirmed in an expansion group to establish the recommended Phase 2 dose. Part 2 of the study will then investigate SON-1010 monotherapy, its use in combination with atezolizumab, or the standard of care (SOC) for PROC in a randomized comparison to show proof-of-concept (POC). Initial safety data from Part 1 of the SB221 study are expected during the first half of 2024.

In September 2023, Sonnet announced the completion of two independent in vivo proof-of-concept (POC) studies to show the biodistribution of interleukin-FHAB molecules to the tumor microenvironment (TME), using labs with expertise in radiolabeling biologics and in vivo biodistribution analysis. The labs employed different radiolabeling methodologies (99mTc or 89Zr) for mIL-12 and mIL12-FHAB. The two studies were completed using the B16F10 mouse melanoma model to measure the accumulation of radiolabeled product and tumor volume inhibition over various time points. Both studies indicated that mIL12-FHAB had significantly higher tumor accumulation, 2.5-4.7 times higher on average at the longer time points, and increased retention when compared to mIL-12. Accumulation was demonstrated in tumors compared to normal mice, and was transient in liver, kidney, and other organs, as expected. Importantly, radiolabeled mIL12- FHAB also demonstrated measurable accumulation in the draining lymph nodes. Overall, these findings have important implications for therapeutic applications of any mono-(ILx-FHAB) or bi-functional (ILx-FHAB -ILy) molecules demonstrating enhanced tumor targeting and accumulation, as well as the potential for improved efficacy that could lead to a variety of drug candidates.

SON-1210 (IL12-FHAB-IL15): In February 2023, Sonnet announced data from two successfully completed IND-enabling toxicology studies with SON-1210 in non-human primates. The compound elicited no serious adverse events in repeat, subcutaneous dosing and was well-tolerated using dosing levels at least 50x higher than the highest anticipated human clinical dose level. Sonnet is prepared to initiate the regulatory authorization process for SON-1210, pending the outcome of any partnering activity.

SON-1410 (IL18-FHAB-IL12): Cell line development and process development are ongoing, with early experimental drug supply suitable for formulation and analytical method development activities. After some delays in 2023, activities will continue into 2024 with the potential to generate a drug suitable for preclinical studies and subsequent human studies.

SON-080 (low-dose IL-6): Enrollment of the first portion of the SB211 study in CIPN is nearing completion, which should position the DSMB to complete its review of the preliminary safety data during the first calendar quarter of 2024.

John Cini, Ph.D., Sonnet’s CSO and Co-founder commented on the fiscal year’s R&D accomplishments, saying, "The biodistribution data we announced in September further confirmed the ability of the FHAB technology to extend therapeutic half-life and potentiate tumor targeting, which, combined with the clinical data we presented at AACR (Free AACR Whitepaper) in April, position the platform as a differentiated approach for developing next-generation, cytokine-based oncologic drugs. We are excited about the opportunity to continue to highlight our pipeline assets at upcoming medical conferences and through the publication of peer-reviewed articles that elucidate our findings."

Financings Completed: On February 10, 2023, we closed a public offering of common stock and certain warrants for net proceeds of $13.6 million through the issuance and sale of 530,222 shares of our common stock and, to certain investors, pre-funded warrants to purchase 101,090 shares of common stock, and accompanying common warrants to purchase up to an aggregate of 1,262,618 shares of our common stock. The public offering price of each share of common stock (or pre-funded warrant in lieu thereof) and accompanying common warrant was $23.76.

On June 30, 2023, we closed a registered direct offering of common stock (and common stock equivalents in lieu thereof) and a concurrent private placement of certain common stock warrants for net proceeds of $1.9 million through the issuance and sale of 166,363 shares of our common stock and, to certain investors, pre-funded warrants to purchase 60,909 shares of common stock, and accompanying common warrants to purchase up to an aggregate of 227,272 shares of our common stock. The offering price of each share of common stock (or pre-funded warrant in lieu thereof) and accompanying common warrant was $9.90.

On October 26, 2023, we closed a public offering of common stock and certain warrants for net proceeds of $4.1 million through the issuance and sale of 1,306,250 shares of our common stock and, to certain investors, pre-funded warrants to purchase 1,537,500 shares of common stock and accompanying common warrants to purchase up to an aggregate of 5,687,500 shares of our common stock. The public offering price of each share of common stock (or pre-funded warrant in lieu thereof) and accompanying common warrant was $1.60.

Fiscal Year Ended September 30, 2023 Financial Results

Jay Cross, CFO, elaborated on Sonnet’s performance, saying, "We are very pleased with the progress we made this year in an otherwise challenging environment for small biotechnology companies. We will continue to closely monitor our operating expenses, and we are happy to share the preliminary approval we recently received to sell up to $4.8 million of our New Jersey state net operating losses."

As of September 30, 2023, Sonnet had no debt and $2.27 million cash on hand, which excludes net proceeds of $4.1 million from the October financing. Sonnet believes its cash at September 30, 2023, together with the $4.1 million net proceeds from the October financing, will fund its projected operations into March 2024. In addition, Sonnet expects to receive a $0.8 million net cash refund from the research and development tax incentive program in Australia and recently received preliminary approval of its application to sell up to $4.8 million of its New Jersey state net operating losses through the Technology Business Tax Certificate Transfer Program, subject to execution of such sale, which together Sonnet believes will extend the funding of its projected operations into the third calendar quarter of 2024.

Research and development expenses were $11.8 million for the year ended September 30, 2023, compared to $21.4 million for the year ended September 30, 2022. The decrease of $9.6 million was primarily due to the establishment of cost savings by transitioning product development activities to cost advantaged locations such as India and Australia, by reducing expenditures on tertiary programs such as SON-3015, which has been placed on a development hold, and suspending antiviral development related to SON-1010, as well as a decrease in share-based compensation expense.

General and administrative expenses were $7.1 million for the year ended September 30, 2023, compared to $8.6 million for the year ended September 30, 2022. The decrease of $1.5 million relates primarily to a decrease in share-based compensation, legal and business development expenses, as we are managing expenses for liquidity purposes and are tightening our focus on the research and development projects we have assessed to have the greatest near-term potential.

On December 14, 2023 SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) ("SELLAS’’ or the "Company"), a late-stage clinical biopharmaceutical company focused on the development of novel therapies for a broad range of cancer indications, reported that the first patients have been enrolled in the 60 mg dose cohort in its ongoing Phase 2a clinical trial of its novel and highly selective CDK9 inhibitor, SLS009, in combination with venetoclax and azacitidine (aza/ven) in patients with relapsed/refractory (r/r) acute myeloid leukemia (AML) who did not respond or stopped responding to venetoclax-based therapies (Press release, Sellas Life Sciences, DEC 14, 2023, View Source [SID1234638575]).

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A total of nine patients have been enrolled at the 45 mg safety dose level. Eight patients remain alive (one patient succumbed to sepsis having previously contracted COVID 19) and six continue treatment. The first enrolled patient achieved a complete response and is currently in the seventh month of treatment and the second enrolled patient is in the sixth month of treatment. Significant anti-leukemic effects (≥50% decrease in bone marrow blasts) were observed during treatment in five out of six assessable patients with no significant safety issues to date. No dose limiting toxicities (DLT) were observed in any of the patients. Topline data for the 45 mg cohort are expected around year-end 2023. Patients with AML that fail venetoclax-based therapies have limited treatment options and a poor prognosis with a median overall survival (mOS) of approximately 2.5 months.

"We are thrilled with the Safety Monitoring Committee advocating that we proceed to the recommended Phase 2 dose level of 60 mg after finding no safety concerns with the 45 mg cohort, which represents important progress in the clinical advancement of SLS009. Based on the encouraging efficacy data and safety profile that continues to emerge in the Phase 2a trial, we remain excited about the potential for SLS009 as a promising treatment option for the many AML patients with poor prognosis and limited alternatives currently available once they become resistant to venetoclax," said Angelos Stergiou, MD, ScD h.c., President and Chief Executive Officer at SELLAS. "To align with the FDA’s Project Optimus initiative, our dosing strategy in this next arm of the Phase 2a trial will include evaluation of two dosing regimens, 60 mg once per week and 30 mg twice per week. We look forward to sharing early data from this cohort as well as further clinical data of the 45 mg cohort around the end of this year or early next year."

The Phase 2a clinical trial of SLS009 is an open label, single arm, multi-center study that is designed to evaluate safety, tolerability, and efficacy at two dose levels, 45 mg and 60 mg, in combination with aza/ven. In the 60 mg dose cohort, patients will be randomized to one of two groups, 60 mg flat (fixed) dose once per week and 30 mg fixed dose two times per week. Each group will enroll 5 – 10 patients. In addition to safety and tolerability of SLS009 in combination with aza/ven, the primary endpoints are composite complete response rate (CRc) and duration of response (DOR). Additional endpoints include event free survival (EFS), OS, and pharmacokinetic (PK) and pharmacodynamic (PD) assessments. Venetoclax combinations with hypomethylating agents are a commonly used regimen in this target population but despite high efficacy (up to ~67% complete response rate), approximately one-third to one-half of patients do not respond to venetoclax based regimens, and among those who respond almost all eventually relapse.

SLS009 was recently granted orphan drug designation by the U.S. Food and Drug Administration in AML supported by the data from the Phase 1 study of SLS009 as a monotherapy that met all key study objectives. In the Phase 1 study one patient with AML achieved a complete response, making SLS009 the first CDK9 inhibitor to achieve a complete response in r/r AML as a monotherapy, and remained alive for 11 months as of the last follow up.

On December 14, 2023 Pfizer Inc. (NYSE: PFE) reported the successful completion of its acquisition of Seagen Inc. (NASDAQ: SGEN), a global biotechnology company that discovers, develops and commercializes transformative cancer medicines (Press release, Seagen, DEC 14, 2023, View Source [SID1234638574]). Pfizer completed its acquisition of all outstanding common stock of Seagen for $229 in cash per share, for a total enterprise value of approximately $43 billion.

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"Cancer remains a leading cause of death, and one in three people in the U.S. will receive a cancer diagnosis in their lifetime. With one of the largest investments in Pfizer’s history, we are going all in on cancer with the goal of delivering breakthroughs that drastically improve the lives of people with cancer," said Dr. Albert Bourla, Pfizer Chairman and Chief Executive Officer. "With Seagen’s proprietary, world-leading Antibody-Drug Conjugate (ADC) technology, together with the scale and strength of Pfizer’s capabilities and expertise, we are poised to change the cancer treatment paradigm. We believe Oncology will be a significant growth driver for Pfizer and contribute meaningfully to the achievement of our near- and long-term financial goals."

Seagen is a world-leader in ADC technology, a transformative modality that is emerging as a powerful tool across a broad range of cancers designed to preferentially kill cancer cells and limit off-target toxicities. With the addition of Seagen’s four in-line medicines, ADCETRIS (brentuximab vedotin), PADCEV (enfortumab vedotin), TIVDAK (tisotumab vedotin) and TUKYSA (tucatinib), Pfizer’s industry-leading Oncology portfolio now includes over 25 approved medicines and biosimilars across more than 40 indications, including nine medicines that are either blockbuster or have the potential to be blockbuster.

With the addition of Seagen, Pfizer’s Oncology pipeline has doubled in size with 60 programs spanning multiple modalities, including ADCs, small molecules, bispecifics and other immunotherapies. Moving forward, Pfizer will leverage its leading protein engineering and medicinal chemistry capabilities to advance Seagen’s ADC technology, unlocking potential novel combinations and next-generation biologics.

"This is a great day for Pfizer, and, more importantly, for people living with cancer, as we bring together the game-changing science and top talent of Seagen and Pfizer to form a leading Oncology organization," said Chris Boshoff, Chief Oncology Officer and Executive Vice President, Pfizer. "Driven by science and a passion for improving and extending patients’ lives, together, we will work with urgency towards our common purpose to deliver transformative cancer medicines and bring new hope to people living with cancer everywhere."

As previously disclosed, to address U.S. Federal Trade Commission concerns, Pfizer has chosen to irrevocably donate the rights of royalties from sales of Bavencio (avelumab) in the U.S. to the American Association for Cancer Research (AACR) (Free AACR Whitepaper). This unrestricted donation will support AACR (Free AACR Whitepaper) in its mission to prevent and cure cancer through research, education, communication, collaboration, science policy, and funding for cancer research.

Guggenheim Securities, LLC served as Pfizer’s financial advisor and Wachtell, Lipton, Rosen & Katz and Arnold & Porter Kaye Scholer LLP served as Pfizer’s legal advisors. Centerview Partners LLC served as Seagen’s financial advisor and Sullivan & Cromwell LLP served as Seagen’s legal advisor. MTS Health Partners also provided financial advice to Seagen.

On December 14, 2023 Haystack Oncology, a Quest Diagnostics (NYSE: DGX) company, reported that it has entered into a collaboration with Rutgers Cancer Institute of New Jersey to use Haystack Oncology’s industry-leading personalized MRD technology (Haystack MRD) to help evaluate therapeutic response and provide molecular insights for a Rutgers Cancer Institute clinical trial examining early-stage triple-negative breast cancer (TNBC) patients undergoing treatment in the adjuvant setting with liposomal doxorubicin and carboplatin (Press release, Quest Diagnostics, DEC 14, 2023, View Source [SID1234638573]). Rutgers Cancer Institute together with RWJBarnabas Health is the state’s only National Cancer Institute-designated Comprehensive Cancer Center.

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"We’re excited to work with Rutgers Cancer Institute in their efforts to optimize therapeutic strategies for patients with early-stage breast cancer," said Dan Edelstein, Vice President and General Manager of Haystack Oncology. "With unparalleled sensitivity, Haystack MRD provides a tool for anticipating and evaluating treatment-related benefits to a greater depth than standard clinical and radiographic metrics, making it well-equipped to support clinical studies such as this, which are essential for advancing cancer care."

"Triple-negative breast cancer is a subtype of breast cancer that is aggressive by nature with a complex biology, therefore, the disease tends to have a worse prognosis," said Mridula George, MD, associate program director of Breast Medical Oncology at Rutgers Cancer Institute and principal investigator of the study, which is also open at select RWJBarnabas Health sites across New Jersey. "We are excited to use Haystack’s MRD technology to monitor treatment response in our clinical trial that could help inform future studies and novel approaches that will result in better outcomes for our patients."

On December 14, 2023 Purple Biotech Ltd. ("Purple Biotech" or "the Company") (NASDAQ/TASE: PPBT), a clinical-stage company developing first-in-class therapies that harness the power of the tumor microenvironment to overcome tumor immune evasion and drug resistance, reported that it has completed patient enrollment in a Phase 2 study of CM24, a multi-functional immune checkpoint inhibitor, for the treatment of pancreatic ductal adenocarcinoma (PDAC) (Press release, Purple Biotech, DEC 14, 2023, View Source [SID1234638572]).

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The Phase 2 study (NCT04731467), in collaboration with Bristol Myers Squibb (BMS), is evaluating CM24 in combination with BMS’s nivolumab plus chemotherapy in PDAC patients as a 2nd line treatment as compared to chemotherapy alone. The primary endpoint is overall survival (OS). Approximately 60 patients have been enrolled through 18 centers in the U.S., Spain and Israel.

The trial was fully enrolled in advance of the anticipated 2024 timeline. An interim analysis of overall survival, the primary endpoint of the study is expected during 1H 2024 and topline analysis is expected in 2H 2024.

"Having completed patient enrollment, we now look forward to reporting overall survival results in 2024. We thank the patients and their families for participating in this important and promising study, which may advance CM24 toward a pivotal study for a population in dire need of an effective alternative. Survival rates in pancreatic cancer are unfortunately very low and with CM24’s novel CEACAM1 target, we believe we may have a positive impact on extending survival," stated Purple Biotech CEO, Gil Efron.

An estimated 60,000 people are diagnosed with pancreatic cancer in the U.S. alone with a 5-year survival rate of only 12%. In patients treated with chemotherapy as a 2nd line treatment, the 5-year survival drops to 3%.