On May 8, 2023 Journal of Hematology & Oncology (JHO, 2022 impact factor of 23.168) published the results of the Phase I clinical study of Qilu Pharma’s immunotherapy bifunctional antibody, QL1706 (J Hematol Oncol. 2023 May 8;16(1):50) (Press release, Qilu Pharmaceutical, MAY 8, 2023, View Source;oncology-301823147.html [SID1234631608]). This study is the first large Phase I clinical trial of QL1706 in humans, and was led by Prof. Li Zhang and his team at Sun Yat-sen University Cancer Center. The results provide further support for the use of dual immunotherapy in patients with advanced solid tumors.

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QL1706 is a bifunctional dual blocker developed by Qilu Pharma using the novel MabPair antibody technology platform to simultaneously produce two engineered monoclonal antibodies in a single cell, the PD-1 IgG4 antibody iparomlimab and the CTLA-4 IgG1 antibody tuvonralimab. The CTLA-4 antibody has a shorter elimination half-life in vivo, with a shorter exposure for CTLA-4 antibodies in a dosing cycle.

A total of 518 patients were enrolled in this study, of whom 99 patients in the Phase I dose escalation study received a single dose of QL1706 (intravenous, every 3 weeks) at 0.3-10 mg/kg to determine the maximum tolerated dose (MTD), Phase II recommended dose (RP2D), safety, pharmacokinetics (PK) and pharmacodynamics (PD) of QL1706. In the Phase Ib study, 419 patients with advanced solid tumors received 5 mg/kg (RP2D) of QL1706 (administered every 3 weeks) to evaluate the preliminary efficacy of QL1706 in the treatment of non-small cell lung cancer (NSCLC), nasopharyngeal carcinoma (NPC), cervical cancer (CC) and other solid tumors.

The incidence of treatment-related adverse events (TRAEs) was 74.9% (388/518) in all patients, with 16% of TRAEs being grade 3 or higher. Thirty (5.8%) patients withdrew from the study due to TRAEs. The most common TRAEs were rash (19.7%), hypothyroidism (13.5%) and pruritus (13.3%). The incidence of immune-related adverse events (irAEs) was 46.1% (239/518) and 8.1% for grade 3 or higher irAEs.

With comprehensive assessment, the RP2D of QL1706 was determined to be 5 mg/kg. In the Phase Ib part, patients were treated with QL1706 at RP2D. The median follow-up was 9.5 months. The objective response rate (ORR) was 16.9% (79/468) and the median duration of response (DoR) was 11.7 months (95% CI, 8.3 – not reached). In cervical cancer, NPC, small cell lung cancer and NSCLC, the ORR was 27.3% (15/55), 24.5% (27/110), 23.1% (6/26) and 14.0% (17/121), respectively. The ORR in immunotherapy-naïve NSCLC, NPC and cervical cancer was 24.2%, 38.7% and 28.3%, respectively.

The Phase I clinical trial of QL1706 has shown that QL1706 is safe and well tolerated. QL1706 showed good ORR in advanced solid tumors and higher ORR in NPC, cervical cancer and lung cancer. QL1706 plus chemotherapy is currently being studied in a number of Phase III clinical trials in cervical cancer, NSCLC adjuvant treatment, advanced NSCLC and NPC.

Prof. Li Zhang from Sun Yat-sen University Cancer Center said, "QL1706 is the first Mabpair product targeting PD-1 and CTLA-4, and the paper published presents the first large phase I study of QL1706 in humans. The results showed that QL1706 was well tolerated in advanced solid tumors and demonstrated good anti-tumor activity in advanced NSCLC, NPC, cervical cancer and other tumors. This study provides strong support for further clinical research of QL1706, which is expected to become a new approach of dual immunotherapy. We hope this innovative dual immunotherapy will be available to patients as quickly as possible."

Ligand has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission .

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On May 9, 2023 Evotec SE (Frankfurt Stock Exchange: EVT, Prime Standard, ISIN: DE0005664809; NASDAQ: EVO) and Sandoz AG, a division of Novartis (NASDAQ: NVS) reported that Evotec’s Seattle-based subsidiary, Just – Evotec Biologics, Inc., launched a multi-year, long-term tech partnership with Sandoz for the immediate development and subsequent manufacturing of multiple biosimilars (Press release, Evotec, MAY 8, 2023, View Source;evotec-biologics-launches-tech-partnership-for-biosimilars-development-and-commercial-manufacturing-6290 [SID1234631242]).

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The partnership includes an option for the non-exclusive in-licensing of Just – Evotec Biologics’ proprietary technology by Sandoz for building its fully-owned S.POD facility (in analogy to Just – Evotec Biologics’ state-of-the-art J.POD facilities). According to the deal, Just – Evotec Biologics will receive a double-digit-million upfront and future payments dependent on successful development progress of US$ 640 m as well as additional undisclosed payments dependent on progress into commercial manufacturing and exercising the S.POD option.

The partnership sets out highest ambitions for reaching highest quality and lowest cost levels by introducing Just – Evotec Biologics’ data-driven, fully integrated design capability and continuous manufacturing technology (J.DESIGN) into the field of biosimilars, exclusive for all molecules in scope. Both parties are closely aligned in their quest for improving access to medicines for patients across the globe. The development of the biosimilars will ramp up over the coming 12-18 months in a highly collaborative fashion at Just – Evotec Biologics’ J.POD facilities.

In addition, this partnership will set a precedent for Sandoz being able to in-license, non-exclusively, the Just – Evotec Biologics’ proprietary J.DESIGN platform, process development and continuous manufacturing technology and build a state-of-the-art, fully owned ‘S.POD’ facility in the latter part of this decade. To secure industry leading performance, the Just – Evotec Biologics team will support design, construction, onboarding, and training of the Sandoz team to fully realise the potential of the technology with positive impact on cost, speed, and quality in the field of biosimilars.

J.DESIGN, Just – Evotec Biologics’ data-driven, highly automated end-to-end biologics technology platform, employs a series of innovative technologies relying on the use of artificial intelligence, machine learning, intensified and continuous bioprocesses. The platform is specifically designed for de-risking clinical development, providing flexible clinical and commercial manufacturing capabilities within the same J.POD facility and ultimately enabling cost-effective biologics commercial supply.

Dr Matthias Evers, Chief Business Officer, Evotec, commented: "We are thrilled to launch this partnership with massive impact potential for patients globally. With Sandoz’ recognised leadership in biosimilars development and commercialisation and our disruptive technology platform in the field of biologics development and manufacturing, this partnership has a chance to shift the paradigm of what it means to achieve access to lifesaving medicines."

Dr Linda Zuckerman, Executive Vice President, Global Head Biotherapeutics at Just – Evotec Biologics, added: "We are excited to build a highly collaborative partnership with a global leader in the field and are fully committed to support the team at Sandoz in development and manufacturing of a broad biosimilars portfolio out of our state-of-the-art J.POD sites. This partnership supports fully our mission to provide global access to important biotherapeutic medicines."

CONFERENCE CALL

Evotec is going to hold a conference call on Wednesday, 10 May 2023 to provide further information regarding this partnership. The conference call will be held in English.

Conference call details

Date: Wednesday, 10 May 2023

Time: 02.00 pm CEST (08.00 am EDT, 01.00 pm BST)

To join via phone, please pre-register via this link. You will then receive a confirmation email with dedicated dial-in details such as telephone number, access code and PIN to access the call.

A simultaneous slide presentation for participants dialling in via phone is available under this link.

On May 8, 2023 InterVenn Biosciences, the life science company pioneering glycoproteomics, presented new data at the 2023 Digestive Disease Week (DDW) annual conference, which was honored as a "Poster of Distinction" (Press release, InterVenn Biosciences, MAY 8, 2023, View Source [SID1234631197]). This data, generated by InterVenn’s novel, proprietary biomarker discovery platform, GlycoVision, analyzed 575 retrospective samples and was able to achieve an overall sensitivity of 89% and specificity of 89% for predicting advanced adenoma (AA) and colorectal cancer (CRC). Separately, AA (N=32) was predicted with 87.5% sensitivity and CRC with 89.4% sensitivity. The sensitivity results of 87.5% for AA prediction is the highest that has been reported to date in the industry.

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"The data presented yesterday validates that we are on the right track toward defining a new era of pre-cancer detection for patients at risk of developing colon cancer," noted Erwin Estigarribia, InterVenn’s CEO. "Our unique glycoproteomic technology has achieved the industry’s highest level of sensitivity and specificity rates for AA and CRC seen to date using liquid biopsy and we expect to have a clinically validated test available to patients on the market later this year."

"We’ve known that aberrant glycosylation events in colonic crypts and systemic circulation occur throughout the adenoma to carcinoma sequence. To put simply, we’ve known for some time of the possibility to detect AA at the pre-cancer stage," said Daniel Hommes, MD, PhD, gastroenterologist, and Chief Medical Officer at InterVenn. "Other non-invasive tests, which primarily analyze circulating tumor cells, have not been able to achieve this level of sensitivity at the AA stage for the fundamental reason that precancerous lesions do not shed tumor DNA. The ability of our platform to measure glycosylation of circulating plasma proteins, detecting precancerous advanced adenomas and early CRC with high sensitivity from very small amounts of peripheral blood (as little as 50 µl of serum or plasma) is a differentiating feature of our technology. We are now thrilled to have data that validates the GlycoVision capabilities in a clinically meaningful way."

GlycoVision allows high resolution and high throughput glycoproteomic profiling by combining liquid chromatography and mass spectrometry (LC-MS) with AI-powered data processing. The platform’s method of assessing circulating serum glycoproteins is unlike any non-invasive test for CRC that’s on the market, which primarily analyze circulating tumor DNA (ctDNA), circulating tumor cells (CTC), or cell-free DNA (CfDNA). While some of these tests can meaningfully detect CRC, their ability to detect AA, when available treatments have a higher rate of success, have remained elusive. GlycoVision can offer a robust pipeline of powerful and broad clinical applications, ranging from early disease screening to diagnostics and even therapeutics, from as little as 50 µl of serum or plasma.

Access InterVenn’s poster "Warning signs from the crypt: Aberrant protein glycosylation marks opportunities for early colorectal cancer detection" here.

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.