On June 28, 2024 Pulse Biosciences, Inc. (Nasdaq: PLSE) (the "Company" or "Pulse Biosciences"), a company leveraging its novel and proprietary CellFX Nanosecond Pulsed Field Ablation (nsPFA) technology, reported the preliminary results of its rights offering, which expired at 5:00 p.m., Eastern Time, on June 26, 2024 (the "Expiration Date") (Press release, Pulse Biosciences, JUN 28, 2024, View Source [SID1234644616]).

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In accordance with the pricing structure described in the prospectus supplement relating to the rights offering, the final subscription price for the units offered (the "Units") is $10.00 per Unit. Each Unit consisted of one share of the Company’s common stock, par value $0.001 per share, and two warrants, each being a warrant to purchase one-half of one share of common stock. Each warrant will be exercisable for $11.00 per whole share, which equals 110% of the subscription price for the Units. Warrants are exercisable immediately and will expire on the fifth anniversary of the completion of the rights offering. Half of the warrants issued in the rights offering are redeemable by the Company if the Company’s stock trading price exceeds $16.50 for twenty consecutive trading days and the other half of the warrants issued in the rights offering are redeemable by the Company if its stock trading price exceeds $22.00 for twenty consecutive trading days.

Based on a preliminary tabulation by Broadridge Corporate Issuer Solutions, Inc. (the "Subscription Agent"), as of the Expiration Date, the Company received basic subscriptions and over-subscriptions in excess of $83 million, equal to approximately 138% of the $60 million limit in the rights offering, and subscriptions from over 800 accounts, including those of the Company’s Executive Chairman, Robert Duggan. Available Units will therefore be allocated proportionately among those rights holders who exercised their over-subscription right based on the number of Units each rights holder subscribed for under its basic subscription rights, in accordance with the procedures described in the prospectus relating to the rights offering, as amended, and the remaining oversubscription amounts will be returned by the Subscription Agent to the investors. The common stock and warrants comprising the Units will separate upon the closing of the rights offering and will be issued individually. The Company expects the Subscription Agent to distribute such shares and warrants, as well as the sale proceeds, as soon as practical upon the closing of the rights offering.

The Company expects to receive aggregate gross proceeds from the rights offering of $60 million, excluding additional proceeds of up to $66 million from the exercise of warrants issued in the rights offering (if any such exercises occur). The results of the rights offering are preliminary and subject to change pending finalization of subscription procedures by the Subscription Agent.

The rights offering was made pursuant to the Company’s registration statement on Form S-3, as modified by the post-effective amendment filed with the Securities and Exchange Commission ("SEC") on May 28, 2024, which was deemed effective by the SEC on May 31, 2024, including the prospectus contained therein, as further modified by the prospectus filed pursuant to Rule 424(b)(2) of the Securities Act of 1933, which contains the detailed terms of the rights offering and was filed with the SEC on June 4, 2024. Copies of the foregoing documents may be obtained at the SEC’s website at www.SEC.gov. Subscription rights that were not exercised by 5:00 p.m., Eastern Time, on June 26, 2024, have expired.

On June 28, 2024 Waypoint Bio (aka "Waypoint"), a biotechnology company pioneering novel cell therapies for solid tumors using in vivo spatial pooled screening technology, reported $14.5 million in seed funding led by Hummingbird Ventures with participation from other institutional investors, including Recode Ventures and pre-seed lead Fifty Years (Press release, Waypoint Bio, JUN 28, 2024, View Source [SID1234644605]).

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The FDA recently approved the first ever cell therapy for solid tumors, yet innovation in this area has been slow given the challenges of the solid tumor microenvironment and difficulty testing therapies in relevant model systems at-scale. Waypoint’s platform – which uniquely combines spatial biology with pooled screening for the purpose of drug discovery – can conduct initial screens of cell therapy designs in vivo and simultaneously measure hundreds of phenotypes at the single cell level, helping illuminate which designs work and why. This novel approach enables the simultaneous measurement of how many cell therapy candidates can navigate multiple aspects of the solid tumor microenvironment, helping guide the engineering of cell therapy designs for the treatment of historically intractable diseases, such as pancreatic cancer.

"Pooled screening is an incredibly powerful technology for drug discovery, but it’s historically been limited to measuring simple cell phenotypes, such as growth or drug resistance. This limits the technology’s value in more complex diseases where interactions between cells and their environment are key, including T cell interactions with solid tumors in cancers," said Xinchen Wang, PhD, Co-founder and CEO. "Our platform turbocharges traditional pooled screening by leveraging spatial biology to generate complex, multivariate and spatial readouts for every perturbation, helping us quickly generate novel drug candidates with a greater probability of clinical success."

"We built our platform so that we could start our discovery process directly in mouse models, skipping the in vitro step while still testing cell therapy designs at high-throughput and lower cost," said David Phizicky, PhD, Co-founder and Chief Scientific Officer. "This scale of in vivo testing allows us to screen many more innovative cell therapy designs with higher potential for clinical translatability. Using spatial biology, we’re able to read out not only which assets show efficacy in vivo, but also why these assets succeed or fail, and which assets match the phenotypes observed from patient samples. This level of detail presents a potential leap forward in cell therapy design."

Waypoint will use its seed financing toward first designing CAR T-cell therapies with superior efficacy against the tumor microenvironment, and later, Treg therapies for autoimmune diseases.

"We’re thrilled to partner with Xinchen and Dave and lead Waypoint Bio’s seed funding, which will accelerate Waypoint’s plans to develop solid tumor cell therapy designs using spatial biology at scale," said Pablo Lubroth, Investor, Hummingbird Ventures. "Waypoint Bio’s founders are part of an extremely unique subset of scientists that understand the wet lab and computational biology equally well, evidenced by how they combine an in vivo spatial pooled screening platform to generate interpretations of disease that open the door for many new therapies for underserved patients."

Waypoint Bio was co-founded by Xinchen Wang and David Phizicky, MIT alum with complementary wet and dry lab backgrounds and a shared vision for leveraging AI, automation and spatial biology to build a next-generation platform for drug discovery that could impact our treatment of intractable disease. They are joined by a team of 11 researchers, scientists and engineers, and a diverse, expert Scientific Advisory Board, comprised of:

Melina Claussnitzer, PhD, Broad Institute of Harvard & MIT
Robbie Majzner, MD, Dana-Farber Cancer Institute
Yvonne Chen, PhD, UCLA
Shantanu Singh, PhD, Broad Institute
Ron Lennox, D.Phil. MBA, Biotech entrepreneur and investor
To learn more about Waypoint Bio, including partnering and career opportunities, please visit waypointbio.com.

On June 28, 2024 Physician scientists from City of Hope, one of the largest cancer research and treatment organizations in the United States, reported that people with metastatic kidney cancer who orally took a live biotherapeutic product called CBM588 while in treatment with immunotherapy and enzymatic tyrosine kinase inhibitors experienced improved health outcomes (Press release, City of Hope, JUN 28, 2024, View Source [SID1234644604]). The phase 1 trial was published today in Nature Medicine.

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Microorganisms in the gut modulate the immune system. City of Hope researchers are now in discussions with the global SWOG Cancer Research Network to design a phase 2/3 trial to assess the City of Hope-identified novel use of CBM588 and microbiome modulation in people with advanced cancer. Sumanta Pal, M.D., professor and vice chair of academic affairs in City of Hope’s Department of Medical Oncology & Therapeutics Research, is slated to be co-leader of the potential phase 2/3 SWOG trial.

"We at City of Hope are the first to demonstrate a live bacterial product’s ability to improve clinical outcomes for patients with kidney cancer treated with immunotherapy. CBM588 could be exciting in cancer treatment because of its potential to enhance the efficacy of immune checkpoint inhibitor-based treatment, improve patient outcomes and modulate the gut microbiota in beneficial ways," said Pal, a City of Hope medical oncologist and corresponding author of the new study. "Ongoing and larger clinical trials are crucial to validate these benefits and address current challenges. If the positive results observed in this small trial and a previous trial with nivolumab and ipilimumab are confirmed, CBM588 could become a valuable supplement in the treatment of various cancers, particularly for patients treated with immune checkpoint inhibitors."

An estimated 44% of U.S. patients with cancer in 2018 were eligible for checkpoint inhibitor drugs, according to a JAMA Network Open article that flags the increasing trend of this percentage.

In the single-center, phase 1 trial, 30 people with metastatic kidney cancer were randomized to receive cabozantinib, an inhibitor of vascular endothelial growth factor receptor, and targeted immunotherapy nivolumab with or without CBM588 as first-line treatment. Participants’ gut microbiome were analyzed via stool samples in the beginning for a baseline and then 13 weeks into treatment.

City of Hope has granted an exclusive worldwide license to Osel for intellectual property on the novel use of CBM588 to enhance the efficacy of checkpoint inhibitors used to treat cancer, including metastatic renal cell carcinoma. Scientists from Osel and Miyarisan Pharmaceutical Co. Ltd, the manufacturer of CBM588, collaborated on the study.

To date, many studies on lung cancer, melanoma and metastatic kidney cancer, among other diseases, have shown that the composition of the gut microbiome could predict immunotherapy outcomes for patients with cancer. Current guidelines for metastatic renal cell carcinoma (kidney cancer) recommend that newly diagnosed patients receive either dual checkpoint inhibitor therapy or a combination of immunotherapy and tyrosine kinase inhibitor, but most patients eventually experience disease progression while on treatment. Positive patient outcomes usually do not last, and subsequent treatments are largely palliative rather than curative. So, physician scientists are looking to combine current strategies with new treatments that do not introduce toxic side effects, such as through microbiome modulation.

In the trial, City of Hope researchers observed an increase in the abundance of unclassified Ruminococcaceae genera, which has been linked with improved clinical outcomes with immune checkpoint inhibitors in recent studies. Clostridium butyricum MIYAIRI 588, the bacterium in CBM588, produces butyric acid, which is critical for intestinal health and is a well-known immunomodulator.

"While not yet part of standard cancer treatment protocols, microbiome modulation is a promising area of research with the potential to enhance the efficacy of cancer therapies, particularly immunotherapies. Current applications are primarily within clinical trials, but the growing body of evidence suggests that microbiome-based interventions may soon become a valuable component of cancer treatment strategies," said Hedyeh Ebrahimi, M.D, M.P.H., City of Hope postdoctoral medical oncology fellow and first author of the study.

City of Hope is accelerating its research on the direct link between a healthy gut and the effectiveness of immune therapies, such as CAR T cell therapy. Its enhanced microbiome program spans from basic to clinical research and includes studying the gut microbiome’s role in protecting transplant patients from complications experienced during their recovery.

"This study demonstrates again that the microbiome has an important role in the efficacy and toxicity of cancer immunotherapy and can be targeted to improve outcome," said Marcel van den Brink, M.D., Ph.D., president of City of Hope Los Angeles and City of Hope National Medical Center, and the Deana and Steve Campbell Chief Physician Executive Distinguished Chair.

The Nature Medicine study entitled "Cabozantinib and nivolumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial" was supported by Exelixis Inc. (XL184-IST123). CBM588 was supplied by Miyarisan Pharmaceutical Co., Ltd. and Osel Inc.

On June 28, 2024 Shorla Oncology (‘Shorla’), a U.S.-Ireland specialty pharmaceutical company, reported that the U.S. Food and Drug Administration (FDA) has approved the company’s New Drug Application (NDA) for TEPYLUTE, a ready-to-dilute formulation to treat breast and ovarian cancer in an easier to prepare, injectable product that enables dosing accuracy (Press release, Shorla Oncology, JUN 28, 2024, View Source [SID1234644603]).

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‘’This approval fulfills an unmet need by addressing the shortcomings and handling complexities of the current lyophilized powder formulation," said Sharon Cunningham, Chief Executive Officer and Co-Founder of Shorla Oncology. "We have taken a vital oncology drug and made it easier for oncology clinics and hospitals to use, while also reducing medical personnel exposure to a hazardous drug."

TEPYLUTE, formerly SH-105, is the third FDA-approved drug for Shorla, and a significant milestone for the company as it seeks approval for several cancer-fighting drugs for the U.S. market.

"The approval of TEPYLUTE represents an important milestone for Shorla as our first in-house developed NDA," said Orlaith Ryan, Chief Technical Officer and Co-Founder of Shorla Oncology.

TEPYLUTE is a liquid form of a well-established, standard of care oncology drug, thiotepa. The new formulation eliminates the need for complex and time-consuming reconstitution. It provides consistent dosing accuracy and allows for "just in time" preparation.2

"Among TEPYLUTE’s many benefits, it removes the necessity to reconstitute which can introduce additional risks of drug preparation errors," emphasized Rayna Herman, Chief Commercial Officer. "We look forward to providing an update on our launch plans for TEPYLUTE in the near future."

The American Cancer Society estimates that more than 300,000 women will be diagnosed with breast cancer in the U.S in 2024.3 About 19,680 women will be diagnosed with ovarian cancer in the United States.4

Shorla Oncology is currently marketing two products with a robust pipeline including SH-201, the first palatable oral liquid treatment for certain forms of leukemia and other cancers. In April, the company announced the FDA had accepted SH-201 for an NDA review with an expected action date of November 30, 2024.

On June 28, 2024 Sirnaomics Ltd. (the "Company", together with its subsidiaries, the "Group" or "Sirnaomics"; stock code: 2257), a leading biopharmaceutical company engaging in discovery and development of advanced RNAi therapeutics, reported that the Group has completed STP707 Phase I clinical study with strong safety profile and stable disease activity for treatment of pancreatic cancer patients (Press release, Sirnaomics, JUN 28, 2024, View Source [SID1234644602]). This is a dose escalation study conducted in 11 oncology clinics in the U.S. The study involved six cohorts, consisting of 50 patients with various cancers, of which 11 had pancreatic cancer.

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In an earlier news release from the Company in August 2023, the Group noted completion of all dosing regimens for its Phase I study of STP707 for the treatment of multiple solid tumors. This basket study has enrolled patients suffering from various types of late-stage cancers and failing after multiple rounds of treatments. The study is to evaluate the safety, tolerability and anti-tumor activity of the Group’s siRNA (small interfering RNA) drug candidate, STP707, through intravenous infusion (IV) with six cohorts of escalating doses. Patients including pancreatic, colorectal, liver, melanoma and other cancers, with advanced/ metastatic or surgically unresectable solid tumors, refractory to standard therapy, were recruited. Six dose levels (3mg, 6mg, 12mg, 24mg, 36mg and 48mg) were explored in ascending doses. Patients received IV infusion on Day 1, 8, 15 and 22 of a 28-days cycle.

11 pancreatic patients (five males and six females, average age 64 years) were enrolled in the study. Patients were heavily pre-treated and received, on average, three lines of therapy prior to enrollment in the study (including Gemcitabine, Paclitaxel and Folfirinox). The preliminary results indicated that the mean treatment cycles completed was three cycles (average 12 doses). The average days for stable disease for all 11 patients with STP707 treatment was 92 days, while 31 days for the 12mg group, 65 days for 24mg group and 112 days for 48mg group, including one patient ongoing at 281 days. No treatment related adverse events (TRAE) were reported for the 11 patients, except for one patient with a Grade 2 infusion reaction. Non-treatment related adverse events were secondary to their advanced metastatic disease including intestinal obstruction, abdominal distention, gastrointestinal obstruction, embolism, gastrointestinal hemorrhage, tumor pain, hypoxia and dyspnea.

The maximum tolerated dose of STP707 for all 50 late-stage cancer patients was not reached even at 48mg dosage level. STP707 was very well-tolerated in a heavily pretreated cancer patient population. The 11 pancreatic subset of patients showed low toxicity and relatively long stable disease at various dosages (106, 281 and 302 days), and warrants further study with STP707 alone or in combination with immune check point inhibitors, given the preclinical documented ability of STP707 to recruit T-cells to the tumor microenvironment (TME). This is the first time a polypeptide nanoparticle-based siRNA cancer therapeutic has demonstrated early positive safety and efficacy results for the treatment of late-stage pancreatic cancer patients.

"We are very excited to see STP707, our leading siRNA drug product for the treatment of heavily pre-treated pancreatic cancer (one of the deadliest tumor types), shows these strong results upon intravenous administration. This is a very promising result for RNAibased cancer therapeutics for the treatment of metastasized tumors." said Dr. Patrick Lu, Ph.D., Founder, Chairman of the Board, Executive Director, President and Chief Executive Officer of Sirnaomics. "The strong safety profile, long-lasting stable disease efficacy and dose-dependent antitumor activity of this intravenously administered STP707 formulation, present a potential novel cancer therapeutic, either as a single drug or in combination with immune check point inhibitor drugs."

For more information about Sirnaomics’ clinical trials please visit ClinicalTrials.gov (Identifier NCT05037149) and the Company’s website at www.sirnaomics.com.

About STP707

STP707 is composed of two siRNA oligonucleotides, targeting TGF-β1 and COX-2 mRNA respectively, formulated in nanoparticles with a Histidine-Lysine Co-Polymer (HKP+H) peptide as the carrier. The specific carrier peptide is distinct from the carrier used in Sirnaomics’ STP705 product. Each individual siRNA was demonstrated to inhibit the expression of their target mRNAs and combining the two siRNA’s produces a synergistic effect that diminishes pro-inflammatory factors. Over-expression of TGF-β1 and COX-2 have been well-characterized in playing key regulatory roles in tumorigenesis. In preclinical studies with STP707, IV administration resulted in knock-down of TGF-β1 and COX-2 gene expressions in various organs including liver, lung and xenograft tumor. In addition, in preclinical models STP707 had shown strong antitumor activity in various solid tumor types. Using a mouse liver orthotopic tumor model, a combination regimen of STP707 with an immune checkpoint antibody has demonstrated a potent antitumor activity.