On May 8, 2023 Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA testing, reported the publication of a new paper in Cancer Cell from the I-SPY2 trial, highlighting the prognostic and predictive utility of Natera’s personalized and tumor-informed, molecular residual disease (MRD) test, Signatera, in locally advanced breast cancer patients receiving neoadjuvant chemotherapy (NAC, treatment before surgery) (Press release, Natera, MAY 8, 2023, View Source [SID1234631196]).

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Up to 50% of newly diagnosed breast cancer patients receive NAC.2 While patients with locally advanced breast cancer can benefit from NAC, response rates tend to be lower among HER2-negative breast cancers, which represent the majority of cases. Such patients are therefore in need of a reliable biomarker predictive of treatment benefit. This study focused on evaluating circulating tumor DNA (ctDNA) dynamics during NAC as a tool to assess response and predict patient outcomes, with the hypothesis that treatment protocols may be tailored to optimize efficacy and reduce exposure to the toxicity of ineffective therapies.

The publication reports on an expanded cohort of 283 patients and 1,024 plasma samples from the I-SPY2 study. Plasma samples were collected at four time points: pretreatment (T0), 3 weeks after initiation of treatment (T1), 12 weeks between paclitaxel-based and anthracycline (AC) NAC regimens (T2), and after NAC before surgery (T3).

Key findings include:

ctDNA-positivity before, during, and after NAC was significantly associated with inferior distant recurrence-free survival (DRFS) in both subtypes (p=0.02 to p<0.0001); and in the 9% of TNBC patients who tested ctDNA-negative pretreatment, zero DRFS events were observed with a median follow-up of 3.12 years.
Early ctDNA clearance at 3 weeks of NAC was a significant predictor of response, as determined by pathologic complete response (pCR) or residual cancer burden (RCB) in TNBC (p=0.0002).
ctDNA-negativity after NAC was significantly associated with improved DRFS, even in patients with extensive residual cancer burden at surgery (p<0.0001), indicating that ctDNA status may be more prognostic than pCR status.
"Neoadjuvant chemotherapy is a powerful tool to optimize treatment of breast cancer. As we introduce new therapies, we need optimal tools to predict complete response," said Laura Esserman, MD, MBA, and Laura van ‘t Veer, PhD, professors at the University of California, San Francisco, and co-authors of the paper. "This latest publication from the ISPY-2 study builds upon our previous findings that tumor-informed ctDNA monitoring has the potential to improve the prediction of response to NAC, and with more data, may allow non-invasive assays to replace core biopsies."

"I-SPY2 provides compelling evidence to support the role of ctDNA in predicting the likelihood of benefit from neoadjuvant chemotherapy for HER2-negative breast cancer," said Minetta Liu, MD, chief medical officer of oncology at Natera. "The data support the use of Signatera to improve risk stratification and potentially guide escalation or de-escalation of systemic therapy in the neoadjuvant treatment setting."

About Signatera

Signatera is a custom-built circulating tumor DNA (ctDNA) test for treatment monitoring and molecular residual disease (MRD) assessment in patients previously diagnosed with cancer. The test is available for both clinical and research use, and has been granted three Breakthrough Device Designations by the FDA for multiple cancer types and indications. The Signatera test is personalized and tumor-informed, providing each individual with a customized blood test tailored to fit the unique signature of clonal mutations found in that individual’s tumor. Signatera is intended to detect and quantify cancer left in the body, at levels down to a single tumor molecule in a tube of blood, to identify recurrence earlier and to help optimize treatment decisions.

On May 8, 2023 MAIA Biotechnology, Inc., (NYSE American: MAIA) ("MAIA", the "Company"), a clinical-stage biopharmaceutical company developing targeted immunotherapies for cancer, reported financial results for the first quarter ended March 31, 2023, and provided a corporate update (Press release, MAIA Biotechnology, MAY 8, 2023, View Source [SID1234631195]).

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"We are thrilled with the advancement of the THIO-101 trial, inclusive of reporting the positive topline data and preliminary survival data from the completed Part A safety lead-in of our ongoing phase 2 trial," said Vlad Vitoc, M.D., MAIA’s Chairman and Chief Executive Officer. "The clinical activity seen with THIO thus far, in addition to its favorable safety and efficacy profiles, puts us one step closer to our goal of treating NSCLC and liver cancer. Additionally, we are proud to have strengthened our balance sheet by completing the follow-on offering. As we progress through the year, we look forward to our plan to share the safety data from Part B randomized efficacy/dose selection and receive IND clearance in the U.S."

Corporate Highlights

Reported positive topline data from the completed Part A safety lead-in of the THIO-101 Phase 2 go-to-market trial in advanced Non-Small Cell Lung Cancer (NSCLC) and commenced recruitment in Part B randomized efficacy/dose selection: Topline data from Part A demonstrated that MAIA’s telomere-targeting agent, THIO, administered in sequential combination with Regeneron’s anti-PD-1 therapy, Libtayo (cemiplimab), were generally well-tolerated.

Reported preliminary survival data in Part A of THIO-101 Phase 2 trial for Non-Small Cell Lung Cancer: As of April 2023, the first two patients enrolled in Part A continued to be alive, approximately 10 and 9 months, respectively, from treatment initiation. Both patients have advanced Stage IV metastatic disease and are heavily pretreated, receiving third and fourth line of therapy, respectively, after previously failing treatment with an immune checkpoint inhibitor.

Reported strong efficacy of THIO in liver in vivo cancer models: Study showed THIO with complete and durable responses in Hepatocellular Carcinoma (HCC), which is the dominant histology in primary liver cancer (90%). When combined with immunotherapy checkpoint inhibitor (CPI), the duration of response was further potentiated. Administration of THIO alone and in combination with CPI generated anti-cancer immune memory. Upon rechallenge with two times more cancer cells and no additional treatment, tumor growth was completely prevented.

Closed common stock public offering: Raised gross proceeds of approximately $5.75 million, before deducting underwriting discounts and offering expenses, in a public offering of 2,555,500 shares of common stock at a public offering price of $2.25 per share.

First Quarter 2023 Financial Results

Cash Position: The Company had cash totaling approximately $7.6 million as of March 31, 2023, compared to $10.9 million in cash as of March 31, 2022. The amount as of March 31, 2023 does not include the net proceeds from the public offering of shares of common stock received subsequent to quarter end.

Research and Development (R&D) Expenses: R&D expenses were approximately $2.2 million for the quarter ended March 31, 2023, compared to approximately $2.1 million for quarter ended March 31, 2022. The increase was primarily related to an increase in payroll and bonus expenses of approximately $0.46 million related to the increased headcount of additional research and development employees offset by a decrease in Clinical and Scientific research fees of approximately $0.23 million due less THIO-101 trial start-up fees, and a decrease in consulting and other fees of approximately $0.12 million. R&D expenses included approximately $0.3 million and $0.3 million of non-cash stock compensation expense in the first quarter of 2023 and 2022, respectively.

General and Administrative (G&A) Expenses: G&A expenses were approximately $2.0 million for the quarter ended March 31, 2023, compared to approximately $1.4 million for the quarter ended March 31, 2022. The increase for the quarter was primarily due to approximate increases in payroll and bonus expenses of $0.3 million, an increase of approximately $0.6 million of other expenses related to the costs of operating as a public company, offset by a decrease in stock-based compensation of approximately $0.2 million and professional fees of approximately $0.1 million. G&A expenses included approximately $0.3 million and $0.4 million of non-cash stock compensation expense in the quarters ended March 31, 2023, and 2022, respectively.

Other Income (Expense): Other income was approximately $0.07 million for the quarter ended March 31, 2023, and other expense for the quarter ended March 31, 2022 was approximately $0.03 million. The increase was primarily related to increases in the Australia research and development incentives of approximately $0.02 million and a gain on the change in the fair value of the warrant liability of approximately $0.02 million, offset by increases to interest expense of approximately $0.005 million.

Net Income (Loss): Net loss was approximately $4.1 million for the quarter ended March 31, 2023, as compared to net loss of approximately $3.9 million for the quarter ended March 31, 2022.

About THIO

THIO (6-thio-dG or 6-thio-2’-deoxyguanosine) is an investigational telomere-targeting agent currently in clinical development to evaluate its activity in non-small cell lung cancer (NSCLC). Telomeres, along with the enzyme telomerase, play a fundamental role in the survival of cancer cells and their resistance to current therapies. THIO is being developed as a second or later line of treatment for NSCLC for patients that have progressed beyond the standard-of-care regimen of existing checkpoint inhibitors.

On May 8, 2023 Temple Therapeutics, a biotechnology company pioneering a female-focused precision medicine approach, presented new in vitro and in vivo data on TTX335o, the first drug candidate from the company’s platform that won the Eurostar Eureka peer-reviewed grant process in 2019 for ovarian cancer, and the novel ovarian cell target, lemur tyrosine kinase 3 (LMTK3) (Press release, Temple Therapeutics, MAY 8, 2023, View Source [SID1234631194]). The new data was provided at a poster presentation at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, which took place on April 14-19, 2023 in Orlando.

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"While survival rates for ovarian cancer are creeping up to the 50% level, it is clear that the vast majority of women are diagnosed too late," said Sanj Singh, CEO of Temple Therapeutics. "It has been referred to as the silent killer by some, and others have described it as the neglected or ignored killer. Despite its lethality as the most dangerous gynecological cancer, the field has been sparsely researched. We are changing that. As we recognize World Ovarian Cancer Day today, we can do better. Our sisters, aunts, spouses, friends, co-workers, mothers, and grandmothers are affected."

TTX335o is based on the breakthrough discovery of LMTK3 and its mechanism of action. Increased levels of LMTK3 have been shown to affect the transcription of genes promoting DNA repair, cell viability, and tumorigenesis which activates cell death pathways specific to cancer cells without harming normal cells.

Preclinical data presented at AACR (Free AACR Whitepaper) 2023 included:

LMTK3 protein was detected in 98% of ovarian cancer tissues collected from 204 patients in various stages and major histology and localized in the nucleus of health cells and in the cytoplasm of tumor cells.
Risk of death among ovarian cancer patients with more cytoplasmic than nuclear LMTK3 levels was particularly high during the first year after diagnosis. This suggests cytoplasmic LMTK3 expression correlates with poor survival which serves as a potential prognostic marker for ovarian cancer patient outcomes (p<.01).
TTX335o specifically targets apoptosis, a major determinant in uncontrolled cell growth in ovarian cancer through a novel integrin (αV/β1), monomeric myeloperoxidase (mMPO), and LMTK3 signaling pathways. Knocking down LMTK3 also induced cell death in ovarian cancer, and more importantly, did not harm normal cells.
In vitro and in vivo studies seem to validate LMTK3 as a specific target and predictor of clinical outcomes in ovarian cancer.
Both nuclear and cytoplasmic LMTK3 expressions correlated with tumor grade and patient survival in cancers such as breast and colorectal cancer. The clinical significance of the LMTK3 gene was tested from 204 early-stage (stage I-II) ovarian cancer patients of all major subtypes. Results from this study revealed a higher cytoplasmic to nuclear localization of LMTK3 correlated with worse overall survival (P<0.01). More importantly, engineered novel target-specific molecules, collectively known as TTX335o, significantly induced ovarian cancer cell death. Strikingly, TTX335o molecules are also effective in cells resistant to chemotherapy (e.g., docetaxel or cisplatin) as in sensitive cells.

"The discovery of this novel target almost five years ago was surprising and exciting because we thought, what if this could be an early detection biomarker," said Dr. Ghassan Saed, Inventor and Lead Researcher and Associate Professor of Gynecology Oncology at Wayne State University and Karmanos Cancer Center in Michigan. "Dr. Helou at Sahlgrenska Cancer Center screened the target across 204 Stage I-II ovarian cancer patient samples and saw firsthand the correlation data of expression of the target and poor prognosis. We knew then this may be a game changer for ovarian cancer because it was present in all major subtypes. We saw the potential for a novel biomarker and an associated target. We developed TTX335o to specifically target LMTK3 pathways that kill tumors without harming normal cells, even at high doses."

"Treatment with TTX335o and other modalities, like siRNA, significantly induced the killing of both chemosensitive and chemoresistant ovarian cancer cells without affecting normal cells in vitro," said Anna Portela, CEO of Xenopat, a spin-off of the Catalan Institute of Oncology (ICO), the Bellvitge Biomedical Research Institute (IDIBELL), and the Bellvitge University Hospital (HUB). "Moreover, we observed this killing as synergistic with both Cisplatin and Taxotere treatment in vitro. We used an A2780 cell line-derived orthotopic xenograft mouse model of ovarian cancer to test the efficacy of specific TTX335o in vivo. Strikingly, TTX335o 20 mg/kg IV dose given in the same dosing schedule and duration as cisplatin showed a 35% tumor reduction. More importantly, in vivo safety studies showed no signs of toxicity of TTX335o, even at a very high dose of 40 mg/kg. With molecule, dose, and schedule optimization in ongoing experiments, we could expect a higher efficacy."

"We have generated a substantial amount of preclinical data demonstrating TTX335o is unlike any other targeted therapy for ovarian cancer or approach," said Dr. Neil Sankar, Chief Medical Officer at Temple Therapeutics. "The addition of a companion diagnostic for early detection, therapeutic impact, and disease progression injects much-needed hope for ovarian cancer patients. Earlier diagnosis and intervention improve patient outcomes. It seems that this target is agnostic across the major histological subtypes which helps to serve the 80% of ovarian cancer patients who do not have the BRCA genes (BReast CAncer)."

Follow the World Ovarian Cancer Coalition on Twitter @ovariancancerco and #NoWomanLeftBehind.

The AACR (Free AACR Whitepaper) 2023 poster is available upon request at [email protected].

On May 8, 2023 Primmune Therapeutics, a biotech company harnessing the power of the innate immune system to treat solid tumors in the advanced cancer setting and to clear human papillomavirus and related pre-cancerous cervical lesions, reported that Primmune’s Senior Vice President & Chief Scientific Officer James Appleman, Ph.D., will present at the 4th STING & TLR-Targeting Therapies Summit being held in Boston, Massachusetts from May 9-11, 2023 (Press release, Primmune Therapeutics, MAY 8, 2023, View Source [SID1234631193]).

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The oral presentation will cover the recent clinical progress of PRTX007, a systemically active, orally administered prodrug of a novel, small molecule toll-like receptor 7 (TLR7)-specific agonist and will evaluate how the unique pharmacology elicited by PRTX007 distinguishes Primmune’s lead candidate from other TLR7 agonists in human cellular models, in non-human primates, and in the clinical setting. The presentation at the Summit will also review how PRX034, the TLR7 agonist systemically delivered by PRTX007, has been shown to induce engagement of the innate and adaptive immune responses while avoiding systemic inflammation in healthy volunteers, and why PRTX007’s favorable profile is expected to correlate with efficacy in cancer therapy.

Presentation Details:

Title: PRTX007, a Novel Orally Administered TLR7 Agonist Prodrug from Primmune Therapeutics for the Treatment of Cancer
Presenter: James Appleman, Ph.D.
Date and Time: Wednesday, May 10 at 10 a.m. ET
Location: Hilton Boston Back Bay

More information on the conference can be found here.

About PRTX007

PRTX007, Primmune’s lead clinical development candidate, is designed to provide well-tolerated, controlled, long-term stimulation of the innate immune response while also potentiating long-term effective innate and adaptive immune responses. PRTX007 administration uniquely activates plasmacytoid dendritic cells (pDCs), leading to a systemic immune poly-IFN response without stimulating production of NF-κB-driven proinflammatory factors like IL-6, TNFα or IL-1β. Activated pDCs directly deliver interferons to target cells by paracrine transfer. Conceptually, this is equivalent to administering a therapeutically effective cocktail of all Type I/III IFNs while avoiding the associated side effects and adverse events. Furthermore, PRTX007 administration leads to systemic activation of anti-tumor effector CD8+ T cells and NK cells. PRTX007 is being rapidly advanced towards clinical trials for solid tumors in the advanced cancer setting and for clearing human papillomavirus-transformed pre-cancerous cervical lesions.

On May 8, 2023 Cullgen Inc., a leading biotechnology company developing small molecule therapeutics based on its proprietary uSMITE platform of targeted protein degradation technology, reported that it has raised $40 million in new financing (Press release, Cullgen, MAY 8, 2023, View Source [SID1234631192]). A $35 million series C financing round was led by AstraZeneca-CICC Venture Capital Partnership ("AZ-CICC"), and included Sincere Capital, Voyagers Capital, Wuxi Capital Group (subject to pending ODI approval), as well as existing shareholder GNI Group Ltd. In conjunction with the series C round, AZ-CICC will have the right to designate a representative to join Cullgen’s board of directors. Concurrent with this financing, GNI Group Ltd. has elected to exercise its outstanding warrants for Cullgen stock, resulting in an additional $5 million in proceeds for Cullgen. The total $40 million financing will support the development of Cullgen’s technology platform and internal pipeline of targeted protein degraders in oncology and other diseases.

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"This new round of financing will enable Cullgen to accelerate development of its promising pipeline of targeted protein degraders featuring novel E3 ligands to potentially introduce new treatment approaches for patients battling cancer," said Dr. Ying Luo, Chairman and CEO of Cullgen. "We are extremely pleased with AstraZeneca’s support, and grateful to all our pre-eminent financial partners for their conviction in Cullgen’s position as world-class targeted protein degradation company."