On April 11, 2024 RenovoRx, Inc. ("RenovoRx" or the "Company") (Nasdaq: RNXT), a clinical-stage biopharmaceutical company developing novel precision oncology therapies based on a local drug-delivery platform, reported the execution of definitive subscription agreements with accredited investors for a private placement which is expected to result in gross proceeds of approximately $11.1 million to RenovoRx, before deducting offering expenses (Press release, Renovorx, APR 8, 2024, View Source [SID1234641913]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The proceeds from this financing, in addition to RenovoRx’s previously announced private placement on January 29, 2024 for gross proceeds of approximately $6.1 million, extend the Company’s cash runway into 2026. The financing allows RenovoRx to advance its lead program, the pivotal Phase III TIGeR-PaC clinical trial in locally advanced pancreatic cancer (LAPC), through the second interim readout and towards completion of the trial. The TIGeR-PaC study is an ongoing randomized multi-center study in LAPC using RenovoRx’s proprietary TAMP (Trans-Arterial Micro-Perfusion) therapy platform to evaluate its first product candidate, RenovoGem, a novel oncology drug-device combination product. The study is comparing treatment with TAMP to the current standard of care (systemic intravenous chemotherapy). RenovoRx expects that the second interim analysis for this study will be triggered by the 52nd event in the trial, which is estimated to occur in late 2024.

Proceeds from the financing are also expected to enable the expansion of the TAMP clinical development pipeline into additional cancer indications.

The definite subscription agreements were executed based on the closing price of RenovoRx’s common stock on April 4, 2024, and the private placement is expected to close on April 11, 2024, subject to customary closing conditions. Newbridge Securities Corporation is acting as sole placement agent for the transaction.

Terms of the Private Placement

In connection with the private placement, the Company will issue 7,912,364 shares of common stock, five-year Series A Warrants to purchase an aggregate of up to 7,912,364 shares of common stock, and two-year Series B Warrants, to purchase an aggregate of up to 3,956,182 shares of common stock, with the Series A Warrants and Series B Warrants together constituting 150% warrant coverage. Investors will pay a purchase price of $1.4075 for each share and associated Series A Warrant and Series B Warrant, with such price being at the market for purposes of Nasdaq Stock Market rules. The Series A Warrants and Series B Warrants are each exercisable for $1.22 per share. The Series B Warrants are callable by the Company after 6 months if certain price and volume thresholds are achieved.

The securities being sold in the private placement have not been registered under the Securities Act of 1933, as amended, or state securities laws and may not be offered or sold in the United States absent registration with the SEC or an applicable exemption from such registration requirements. The Company has agreed to file a registration statement with the SEC covering the resale of the shares and the shares underlying the Series A Warrants and Series B Warrants issuable in connection with the private placement.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such jurisdiction.

On April 8, 2024 Tempus, a leader in artificial intelligence and precision medicine, reported that it will present new data along with Pfizer at the AACR (Free AACR Whitepaper) 2024 Annual Meeting (Press release, Tempus, APR 8, 2024, View Source [SID1234641912]). The abstract, titled "Analysis of HER2 prevalence by RNA expression across solid tumors," found that by correlating HER2 protein levels by IHC/ISH and ERBB2 mRNA levels by NGS in tumors of patients with locally advanced/metastatic (LA/m) breast and gastric cancer, RNA expression in several solid tumors apart from breast or gastric cancer may correspond to HER2 IHC≥1+. These findings may open up potential therapeutic routes for HER2-directed antibody-drug conjugates in several tumor types.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

In 2022, Seagen (acquired by Pfizer in December 2023) engaged Tempus to investigate cohorts of patients with HER2 RNA expression. As part of the collaboration, Tempus’ computational and real-world evidence teams helped provide insights on the prevalence of HER2 expression in select solid tumors. Pfizer is leveraging Tempus’ multimodal database to further its HEOR and Translational Science team’s research efforts.

"We’ve been fortunate enough to work alongside the Pfizer team as they expand their understanding of HER2 expression in solid tumors, which outside of breast and gastric cancers, has not been previously well described," said Ryan Fukushima, Chief Operating Officer of Tempus. "For this specific study, we were able to tap into our existing database and analyze 4,500 de-identified records to support their research."

On April 8, 2024 EpiBiologics, a preclinical stage company advancing new bispecific antibody therapeutics for extracellular protein degradation, reported on its EpiTAC protein degraders in oncology demonstrating robust in vivo anti-tumor activity and survival benefit (Press release, EpiBiologics, APR 8, 2024, View Source [SID1234641911]). EpiTAC bispecific antibodies leverage cell-surface degrader receptors enriched in disease tissue to selectively degrade membrane and extracellular targets and address significant unmet needs.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

These data are being presented this morning at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024 in poster presentation #1866, "Discovery of mutation-independent EGFR degrading bispecific antibodies that suppress tumor growth in preclinical tumor models" with Jon Sitrin, Ph.D., Head of Translational Science for EpiBiologics as lead author.

Current cancer treatments targeting EGFR often yield limited benefits due to target-related toxicities and reduced effectiveness in patients with acquired resistance. Recognizing the importance of improving therapeutic outcomes, EpiBiologics tested the efficacy of its novel EpiTACS on this oncogenic driver.

"Our proof-of-concept data demonstrate that EpiTAC activity is greater than standard of care in multiple preclinical tumor models. EpiTAC degradation of EGFR is mutation-independent and can overcome resistance mechanisms. These data motivate us to develop new and clinically meaningful therapies," said Shyra Gardai, Ph.D., Chief Scientific Officer of EpiBiologics.

Poster Presentation Highlights

EpiTACs are bispecific antibodies with a target binding arm and degrader binding arm that together localize degradation of extracellular and membrane targets to disease tissue, sparing normal tissue and increasing efficacy
Novel EpiTACs were rapidly selected and tested using the EpiAtlas of 270+ tumor- and tissue-specific degraders, including transmembrane E3 ubiquitin ligases, chemokine/cytokine receptors and tissue-enriched internalizing receptors
EpiTACs drove robust in vitro tumoricidal activity in colorectal cancer (CRC) and non-small cell lung cancer (NSCLC) models, independent of KRAS or EGFR mutational status
In vivo tumor models demonstrated EpiTACs degraded mutant EGFR and disrupts downstream signaling, suppressing tumor growth and increasing survival beyond osimertinib standard of care
"We believe EpiTACs are a promising new modality, especially for difficult-to-drug targets," said Ann Lee-Karlon, Ph.D., President and CEO of EpiBiologics. "Our modular bispecific antibodies coupled with our EpiAtlas allow us to rapidly screen and manufacture EpiTACs that drive deep anti-tumor responses. We’re committed to advancing EpiTACs for diverse targets in oncology and other disease areas as we move quickly toward the clinic."

On April 8, 2024 AbCellera (Nasdaq: ABCL) reported new data on its T-cell engager (TCE) programs at the American Association for Cancer Research (AACR) (Free AACR Whitepaper)Ⓡ (AACR) (Free AACR Whitepaper) Annual Meeting 2024 at the San Diego Convention Center, with three posters being presented on April 8 and one on April 9. Together, AbCellera’s data demonstrate that it is well-positioned to advance TCEs as a drug class by widening the therapeutic window, enhancing potency, and broadening the accessible target space (Press release, AbCellera, APR 8, 2024, View Source [SID1234641910]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"TCEs are among the most promising new modalities in cancer therapy, but limitations in efficacy and safety have been barriers to realizing their potential for solid tumor indications," said Bo Barnhart, Ph.D., VP, Translational Research at AbCellera. "Our data illustrate that we can repeatedly generate TCEs that maximize tumor-cell killing without inducing excessive cytokine release. Reducing the risk associated with CD3 engagement could improve efficacy both by widening the therapeutic window and by creating opportunities to further enhance potency through co-stimulatory modalities."

AbCellera’s poster presentations, which are available for viewing here, describe how AbCellera is:

Widening the therapeutic window: AbCellera’s data describe the generation of TCEs for three solid tumor targets, PSMA, B7-H4, and 5T4, with functional profiles that are differentiated from clinical benchmarks. These molecules were engineered using a specific set of rare CD3-binding antibodies that consistently show potent tumor-cell killing and low cytokine release across multiple targets, demonstrating their potential to expand the therapeutic window across solid tumor indications.

Enhancing potency: TCEs that engage the CD28 costimulatory receptor can enhance T-cell activation, proliferation, and anti-tumor activities, particularly in solid tumors. The data show that AbCellera’s IgG and heavy chain-only CD28-binding antibodies do not display superagonist activity — a property associated with toxicity. Integrating costimulatory building blocks into AbCellera’s TCE repertoire may enable development of molecules with enhanced potency for difficult-to-treat cancers.

Broadening the accessible target space: The target repertoire for TCEs has been restricted to proteins expressed on the surface of cancer cells. Intracellular peptides displayed on MHC class I (pMHCs) would greatly expand the target pool for TCEs. However, development of TCEs against pMHCs has been limited due to the high degree of target specificity required. Data illustrate how AbCellera is unlocking this target class by generating molecules with high specificity for MAGE-A4-pMHC, which showed little to no binding to hundreds of off-target pMHCs.

"Our platform for creating precision TCEs to address indications in cancer and autoimmunity provides a strong foundation for both internal programs and strategic partnerships," said Murray McCutcheon, Ph.D., SVP, Partnering at AbCellera. "We look forward to advancing these programs with the aim of delivering powerful new medicines for patients."

On April 8, 2024 PanTher Therapeutics ("PanTher" or the "Company"), a clinical-stage oncology company developing high-dose, long lasting, localized treatments for cancer, reported positive data from a first-in-human study of PTM-101, a highly potent chemotherapeutic agent (paclitaxel) combined with an absorbable polymer formulated as a flexible film, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, taking place April 5-10th in San Diego (Press release, PanTher Therapeutics, APR 8, 2024, View Source [SID1234641909]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

This first-in-human study enrolled three patients at a single center in Australia to assess the safety and surgical feasibility of a single, low-dose treatment of PTM-101. PTM-101 was placed directly onto the pancreas, overlying the location of the tumor using standard laparoscopic equipment as part of a disease staging assessment. Once in place over the tumor site, PTM-101 locally delivered a sustained dose of the chemotherapeutic agent over four weeks. Approximately three weeks after placement of PTM-101, all participants began standard of care therapy, which included treatment with mFOLFIRINOX.

Results of the clinical trial demonstrated that PTM-101 reduced the size of pancreatic tumors in all three patients. During the 24 weeks of the prospective phase of the study, the reduction in tumor thickness beneath PTM-101 ranged from 16% to 26%. Two patients had a significant reduction in overall tumor volume (40% and 70%). PTM-101 was also shown to have a favorable safety profile, as it was well-tolerated with no peritonitis, pancreatitis, infection, or hematological toxicity. The chemotherapeutic agent remained localized to the pancreas in all patients, with no detection of systemic paclitaxel at any timepoint.

"Historically, there have been significant clinical challenges realizing the benefits of chemotherapeutics when they are administered systemically. Maintaining a high drug concentration is limited by the route of administration as well as toxicity, which negatively impacts the effectiveness of the drug," said Laura Indolfi, PhD, Chief Executive Officer, and co-founder of PanTher Therapeutics. "We are encouraged by the early clinical data of PTM-101 in patients with locally advanced pancreatic cancer, further validating the potential of our Sagittari platform to deliver high-concentrations of drug directly to the site of a tumor for an extended period of time, without commonly observed undesired side effects."

"Use of PTM-101 to locally administer a highly potent drug, without the limitations from systemic safety and tolerability issues, offers the potential to facilitate significant improvement in patient outcomes, which is clearly needed in the treatment of pancreatic cancer," said Charles Pilgrim, MD, PhD, Associate Professor of Surgery at the Alfred Central Clinical School at Monash University, and principal investigator of the PTM-101 phase 1 clinical trial. "The ability of PTM-101, in combination with standard of care chemotherapy, to shrink pancreatic tumors as observed in this initial study is promising. The prognosis for patients with pancreatic cancer can be particularly devastating, as it is often detected at an advanced stage, at which point there are limited treatment options. Given the trajectory for this cancer, I am very encouraged by the results from the clinical trial of PTM-101 in locally advanced cases and the ease of integrating the treatment into current clinical practice and standard laparoscopic procedures."

PanTher presented a second poster at AACR (Free AACR Whitepaper) describing the non-clinical development of PTM-101.

Both posters are available on the PanTher Therapeutics website.