On October 23, 2021 Turning Point Therapeutics, Inc. (NASDAQ: TPTX), a precision oncology company developing next-generation therapies that target genetic drivers of cancer, reported the presentation of early clinical data from the ongoing Phase 1/2 CARE study in pediatric and young adult patients with advanced solid tumors harboring ALK, ROS1 or NTRK alterations (Press release, Turning Point Therapeutics, OCT 23, 2021, View Source [SID1234591834]). These data are being presented today at the virtual 53rd Congress of the International Society of Paediatric Oncology (SIOP) being held October 21-24.

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"These early data for repotrectinib demonstrate encouraging clinical activity in this pediatric patient population," said Mohammad Hirmand, M.D., chief medical officer. "Patient enrollment is continuing in the Phase 1/2 CARE study, and we look forward to further advancing the development of repotrectinib in this patient population."

Early Data from Phase 1/2 CARE Study
The primary objective of the Phase 1 dose escalation portion of the study is to evaluate the safety and tolerability and determine the recommended Phase 2 dose (RP2D) of repotrectinib in pediatric patients less than 12 years old. The primary objective of the Phase 2 portion of the study is to determine the anti-tumor activity of repotrectinib in pediatric and young adult patients less than 25 years old. Repotrectinib is administrated in capsule or suspension formulation using weight-based dosing for patients less than 12 years old. Patients 12 to 25 years old can enroll directly into the Phase 2 portion of the study with a repotrectinib dose of 160 mg QD for the first 14 days and may increase to 160 mg BID thereafter.

The early Phase 1/2 CARE dataset utilizes an August 2, 2021 data cutoff date. Ten patients were treated across two dose levels. The safety analysis includes the ten treated patients, and the preliminary efficacy analysis includes eight evaluable patients. Patients included in the efficacy analysis had baseline measurable disease and at least one post-baseline evaluable scan. Response evaluation was by physician assessment and per RECIST v1.1 or RANO for CNS tumors. Responses were confirmed with a subsequent scan at least 28 days later.

The findings were reported in a pre-recorded presentation by Steven G. Dubois, M.D., associate professor of Pediatrics, Harvard Medical School available on October 23 at 9:12 a.m. ET on the meeting website.

Preliminary Safety Analysis (n=10) and Pharmacokinetic Analysis

Repotrectinib was generally well tolerated.

The most frequently reported treatment-emergent adverse events (TEAEs) were anemia (n=5) and fatigue (n=5). Among patients with anemia, three had baseline history of anemia.

Dizziness events (n=4) were grade 1 or 2 and none led to treatment discontinuation.

No patients discontinued treatment due to reasons other than disease progression and no patients had TEAEs that led to dose reduction.

No dose-limiting toxicities were reported.

Preliminary pharmacokinetics data indicated that the exposure of repotrectinib in different age groups was comparable to the adult exposure at steady-state.
Preliminary Efficacy Analysis (n=8)

Eight patients were evaluable for efficacy, including four TKI-naïve and four TKI-pretreated patients. TKI-naive patients included those with NTRK amplified anaplastic ependymoma (n=1), NTRK fusion glioblastoma multiforme (GBM)/high grade glioma (n=1), NTRK fusion sarcoma (n=1), and ROS1 fusion inflammatory myofibroblastic tumor (IMT) (n=1). TKI-pretreated patients included those with NTRK fusion GBM/high grade glioma (n=2), NTRK fusion mesoblastic nephroma (n=1), and NTRK fusion sarcoma (n=1).

Three TKI-naïve patients (2 NTRK fusion solid tumors; 1 ROS1 fusion IMT) achieved confirmed responses. One of the three responding patients had a NTRK fusion GBM/high grade glioma, was previously treated with tumor resection, whole brain radiotherapy, and multi-agent chemotherapy, and achieved a complete response (CR) and remained in a response for 3.8+ months as of the data cutoff date. The other two confirmed responders remained in response with duration of response of 7.3+ and 12.1+ months, respectively.

Of the four TKI-pretreated patients, one patient with NTRK fusion sarcoma had a best response of stable disease.
The Phase 1 dose finding portion of the study is ongoing in pediatric patients less than 12 years old to confirm the pediatric RP2D. The Phase 2 portion of the study is ongoing for patients 12 to 25 years old.

Turning Point also announced the publication of preclinical data of repotrectinib in neuroblastoma, the most common pediatric extracranial solid tumor, in the American Association of Cancer Research’s peer reviewed journal, Molecular Cancer Therapeutics. Preclinical studies described in the publication titled "Translational Strategies for Repotrectinib in Neuroblastoma" show that repotrectinib inhibits tumor growth and prolongs survival in patient-derived neuroblastoma xenograft models. In addition, the studies indicated that combining repotrectinib with chemotherapy may be a promising treatment paradigm for neuroblastoma patients.

On October 23, 2021 NANOBIOTIX (Euronext: NANO – NASDAQ: NBTX – the ‘‘Company’’), a late-stage clinical biotechnology company pioneering physics-based approaches to expand treatment possibilities for patients with cancer, reported first ever survival data from its priority head and neck cancer development program at the 2021 Annual Meeting of the American Society for Radiation Oncology (ASTRO) (Press release, Nanobiotix, OCT 23, 2021, View Source [SID1234591835]).

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As specified by the ASTRO Annual Meeting embargo policy, "information beyond what is included in the abstract, such as updated or additional results, is embargoed until the date and time of scientific presentation or presentation at an ASTRO news briefing, whichever occurs first." However, Nanobiotix has become aware that ASTRO made a late decision to release the posters at the same time as the abstracts and did not sufficiently update the embargo policy. As a result, the Company is releasing this data in advance of its intended embargo date.

New Data from Locally Advanced Head and Neck Squamous Cell Carcinoma (LA-HNSCC) Program

Data show a median Overall Survival (mOS) of 18.1 months and a median Progression Free survival of (mPFS) of 10.6 months in the evaluable population (n=41) from the dose expansion part of its phase I, multicenter, open-label, non-randomized dose escalation and dose expansion study evaluating NBTXR3 as a single-agent activated by radiotherapy in tough-to-treat elderly and frail LA-HNSCC patients ineligible for cisplatin and intolerant to cetuximab (Study 102 Expansion). In the full population (all evaluable and non-evaluable patients treated; n=54), data showed a 14.1-month mOS and a 9.4-month mPFS. The data suggest that lower mOS and mPFS observed in the full population versus the evaluable population in the study could be related to early death associated with high burden of comorbidity in the non-evaluable population.

Evaluability in Study 102 Expansion was determined based on the patient receiving at least 80% of the intended intratumoral dose of NBTXR3, at least 60 Gy of radiotherapy, and the required imaging to assess the target lesion at baseline and at least once post treatment.

Response rates remained consistent with previously reported results from the dose escalation and dose expansion study, showing a best observed target lesion objective response rate (ORR) of 85.4% and a best observed target lesion complete response rate (CRR) of 63.4%2.

"I have held the belief that NBTXR3 could have a real impact for patients with solid tumors since reviewing the proof-of-concept data from the phase II/III in soft tissue sarcoma and throughout my participation in Study 102 Expansion," said study principal investigator Professor Christophe Le Tourneau, senior medical oncologist and head of the Department of Drug Development and Innovation (D3i) at Institut Curie. "This first look at survival data has added to my confidence that NBTXR3 could provide a promising new therapeutic option for the practice. I look forward to leading the upcoming phase III global registration study, and to have the opportunity to evaluate the promise of this innovation in a larger patient population."

Of the 21 evaluable patients with a best observed overall response of complete response (CR) with a mean follow-up of 16.1 months, 6 patients died for non-oncologic reasons and only one died from disease progression.

NBTXR3 administration was feasible and well-tolerated overall. A total of 8 Grade 3-4 NBTXR3-related adverse events (AEs) were observed in 8 patients, representing 1.3% of all observed AEs. Of these AEs related to NBTXR3, 5 serious adverse events (SAEs) were observed including dysphagia, sepsis, soft tissue necrosis, stomatitis, and tumor hemorrhage. Of the SAEs, one death from sepsis assessed by the investigator as possibly related to NBTXR3, radiotherapy, and cancer was observed.

While the incidence of LA-HNSCC has continued to rise, patients in the elderly and frail LA-HNSCC population have significant unmet needs. Many are not eligible to receive concurrent chemoradiation due to frailty associated with comorbidities. The modified Charlson Comorbidity Index (mCCI) is a measure of comorbidity burden on a patient-by-patient basis, and high mCCI (i.e., mCCI ≥ 4) is correlated with higher risk of death relative to the broader population. In this study, 63% of all patients treated had high mCCI, which is two to three times the prevalence of comorbidity in the overall LA-HNSCC population3.

Despite the prevalence of high mCCI in Study 102 Expansion, these preliminary data support further evaluation of NBTXR3 activated by radiotherapy as a therapeutic option that may translate to a survival benefit for elderly and frail LA-HNSCC patients. The data also suggest that the potential benefits of the therapy could improve in a population with a lower burden of comorbidity.

"Bringing innovation to the patients that need it most has always been the backbone of our development strategy for NBTXR3," said Laurent Levy, co-founder and chief executive officer of Nanobiotix. "We started with soft tissue sarcoma—a disease indication notoriously resistant to radiotherapy. After proving we could provide a therapeutic benefit versus radiotherapy alone for patients with locally advanced disease and achieving European market approval, we pivoted to patients with locally advanced head and neck cancer that have substantially limited treatment options. The new survival data we are seeing from Study 102 Expansion bolster our confidence in the promise of NBTXR3 as we near the launch of our pivotal phase III study in head and neck cancer. We have designed this study with the benefit of our learnings from the phase I and look forward to the opportunity to prove that our product candidate can expand treatment possibilities for patients with cancer around the world."

About NBTXR3

NBTXR3 is a novel, potentially first-in-class oncology product composed of functionalized hafnium oxide nanoparticles that is administered via one-time intratumoral injection and activated by radiotherapy. The product candidate’s physical mechanism of action (MoA) is designed to induce significant tumor cell death in the injected tumor when activated by radiotherapy, subsequently triggering adaptive immune response and long-term anti-cancer memory. Given the physical MoA, Nanobiotix believes that NBTXR3 could be scalable across any solid tumor that can be treated with radiotherapy and across any therapeutic combination, particularly immune checkpoint inhibitors.

NBTXR3 is being evaluated in locally advanced head and neck squamous cell carcinoma (HNSCC) as the primary development pathway. The company-sponsored phase I dose escalation and dose expansion study has produced favorable safety data and early signs of efficacy; and the launch of a phase III global registrational study is planned. In February 2020, the United States Food and Drug Administration granted regulatory Fast Track designation for the investigation of NBTXR3 activated by radiation therapy, with or without cetuximab, for the treatment of patients with locally advanced HNSCC who are not eligible for platinum-based chemotherapy—the same population being evaluated in the planned phase III study.

Nanobiotix has also prioritized an Immuno-Oncology development program—beginning with a Company sponsored phase I clinical study evaluating NBTXR3 activated by radiotherapy in combination with anti-PD-1 checkpoint inhibitors for patients with locoregional recurrent or recurrent/metastatic HNSCC and lung or liver metastases from any primary cancer eligible for anti-PD-1 therapy.

Given the Company’s focus areas, and balanced against the scalable potential of NBTXR3 , Nanobiotix has engaged in a strategic collaboration strategy with world class partners to expand development of the product candidate in parallel with its priority development pathways. Pursuant to this strategy, in 2019 Nanobiotix entered into a broad, comprehensive clinical research collaboration with The University of Texas MD Anderson Cancer Center to sponsor several phase I and phase II studies to evaluate NBTXR3 across tumor types and therapeutic combinations.

On October 22, 2021 Egle Therapeutics SAS (Egle), an emerging biotechnology company focused on developing First-In-Class immunotherapies targeting immune suppressor regulatory T-cells (Tregs) for oncology and autoimmune diseases, reported that it has completed a €40M ($46.4M) Series A financing (Press release, Egle Therapeutics, OCT 22, 2021, View Source [SID1234591777]). The Series A was co-led by LSP and Bpifrance through their InnoBio 2 fund. Fund+, Bioqube Ventures and Takeda Ventures, Inc. also participated in this round.

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Egle Therapeutics was founded in early 2020 with a vision to become a game changer in the field of Tregs immunomodulation through the unique concept of Tregs starving and specifically targeting the most immunosuppressive ones. Spun out of Institut Curie, Egle’s scientific foundation leverages unprecedented, computational-based, IL-2 modified variants and newly tumor-associated Treg targets to build a furnished pipeline of First-In-Class immunocytokines against Tregs. The new capital will be used primarily to advance 2 leads assets into the clinic and further strengthen its internal drug pipeline.

"Closing a substantial Series A of €40M from a high-quality syndicate of renowned investors, as well as a partnership with a top big pharma like the one we have announced with Takeda in June 2020, all in less than 18 months, puts Egle on a trajectory to execute its vision of tackling regulatory T cells to restore immunity in patients suffering from cancer and autoimmune diseases" commented Luc Boblet, co-founder and CEO of Egle. "The funding will give us appropriate resources to push the first Treg starvers into the clinic and we feel very privileged to undertake such responsibility for the benefit of the whole patient community".

The investor syndicate will join the Egle Therapeutics Board which will consist of Felice Verduyn-van Weegen (LSP), Vincent Brichard (LSP), Jean-Francois Morin (Bpifrance – InnoBio 2) and Sacha Mann (Takeda Ventures). Philippe Monteyne (Fund+), Jacques Mizrahi (Bioqube Ventures) and Elisa El Nouchi (Bpifrance InnoBio 2) will join as observers.

"Egle represents a strategic investment in a First-In-Class technology platform based on innovative research with novel T regulatory modulations and potential in the oncology and auto-immunity fields", commented Vincent Brichard, Venture Partner at LSP. "We feel privileged to be part of such an exciting company, with world class science and look forward to build it out together with the team" adds Felice Verduyn-van Weegen, partner at LSP.

"InnoBio 2 strives to invest in breakthrough ideas and to promote First-In-Class drugs candidates. We are delighted to have co-led a financing round that will enable Egle Therapeutics to broadly invest in its platform technologies, development programs, people and ultimately, towards delivering a pioneering new generation of immunotherapies to patients in need," said Jean-François Morin, Investment Director at Bpifrance.

On October 22, 2021 The Board of Directors of Alligator Bioscience AB (publ) ("Alligator" or "the Company") reported that it has previously, subject to approval by the Extraordinary General Meeting on 8 November 2021, resolved to carry out a rights issue of shares with preferential rights for the Company’s existing shareholders of approximately SEK 257 million (the "Rights Issue") (Press release, Alligator Bioscience, OCT 22, 2021, View Source [SID1234591762]). Through the press release issued on 7 October 2021 regarding the board’s decision to carry out the Rights Issue, Alligator announced that all members of the Company’s board and management with shareholdings in the Company had expressed their intention to subscribe for their respective pro rata share in the Rights Issue, in addition to the other subscription- and guarantee commitments already entered into, which secure the Rights Issue to 100 percent. Alligator hereby announces that all members of the Company’s board and management with shareholdings in the Company now have, via subscription commitments, formally undertaken to subscribe for their respective pro rata share in Rights Issue.

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Through the press release issued on 7 October 2021 regarding the board’s decision to carry out the Rights Issue, Alligator announced that the Company had received subscription commitments from a selection of the Company’s larger existing shareholders, including AP4, Roxette Photo NV and Omentum S.A. In the press release it was also announced that all members of the Company’s board and management with shareholdings in the Company had expressed their intention to subscribe for their respective pro rata share in the Rights Issue. Since the announcement, the Company has now received subscription commitments from all members of the Company’s board and management with shareholdings in the Company, including Søren Bregenholt (CEO), Anders Ekblom (Chairman of the board), Marie Svensson (CFO), Peter Ellmark (CSO), Veronica Wallin (board member) and Hans-Peter Ostler (board member), to subscribe for their respective pro rata share in the Rights Issue, amounting to a total of approximately SEK 0.7 million, which means that the Company has received subscription commitments amounting to a total of approximately SEK 44 million in connection to the Rights Issue, corresponding to approximately 17 percent of the Rights Issue. No compensation is paid for received subscriptions commitments.

For more information regarding the Rights Issue, see the Company’s press release issued on 7 October 2021 and the prospectus (the "Prospectus") that the Company is expected to publish around 9 November 2021.

Advisers

DNB Markets, a part of DNB Bank ASA, Sweden Branch and Redeye AB act as Joint Global Coordinators in connection with the Rights Issue. Setterwalls Advokatbyrå AB acts as legal adviser to Alligator and Baker & McKenzie Advokatbyrå KB acts as legal adviser to the Joint Global Coordinators in connection with the Rights Issue. Aktieinvest FK AB acts as the issuing agent in the Rights Issue.

On October 22, 2021 Invitae (NYSE: NVTA), University College London (UCL), and the Francis Crick Institute reported new data from their TRACERx lung cancer research collaboration funded by Cancer Research UK and sponsored by UCL (Press release, Invitae, OCT 22, 2021, View Source [SID1234591778]). The data, presented by Professor Charles Swanton of UCL and the Francis Crick Institute at the International Society of Liquid Biopsy (ISLB) Congress, further validate the value of liquid biopsy as a less invasive and more comprehensive approach to guiding personalized cancer treatment in the absence of detectable disease by clinical imaging. Previously reported findings from the TRACERx cohort found that monitoring for cancer circulating tumor DNA (ctDNA) based minimal residual disease (MRD) detected relapse of non-small cell lung cancer (NSCLC) up to three years earlier than standard of care imaging surveillance in some instances.1

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Invitae’s (NVTA) mission is to bring comprehensive genetic information into mainstream medical practice to improve the quality of healthcare for billions of people. www.invitae.com (PRNewsFoto/Invitae Corporation)

The study used a new blood-based informatic tool called ECLIPSE (Extraction of CLonality from LIquid bioPSiEs) with an earlier iteration of the Invitae Personalized Cancer Monitoring (PCM) liquid biopsy assay to analyze plasma samples of patients in the TRACERx study. With this approach, data demonstrated multiplex-anchored PCR sequencing of the plasma samples enhanced MRD lead times relative to standard of care surveillance scanning and allowed holistic sampling of clonal dynamics, or tumor heterogeneity, with prognostic implications for disease progression.

"Tumours are highly heterogeneous and standard biopsies can miss important tumor traits. Our findings from applying our novel ECLIPSE software with Invitae’s multiplex-anchored PCR technology, which powers the Invitae PCM assay, are promising. They underscore the tremendous potential of PCM for providing representative tumor sampling throughout the disease course, and most importantly at an early stage or at early recurrence in the absence of disease on standard imaging, which may in the future inform clinical trial stratification and the best treatment plans for patients," said Professor Charles Swanton, Cancer Research UK’s Chief Clinician and a 2021 ISLB award recipient for outstanding scientific contribution in liquid biopsy. "Better understanding the true pathology of a patient’s tumor, including driver and passenger clonal mutations, and identifying MRD earlier, are key to unlocking personalized cancer care and changing the paradigm of cancer drug development towards earlier intervention in the adjuvant setting where cures are more readily achievable."

Invitae’s PCM is a pan-cancer, tumor-informed liquid biopsy assay that uses next-generation sequencing powered by Anchored Multiplex PCR (AMP) to monitor MRD with high sensitivity at low variant allele fractions. The service employs a combination of a tumor profile, blood tests and personalized assays based on a patient’s tumor with the goal of earlier detection of cancer recurrence through ctDNA before it is detectable by imaging or other conventional methods. ECLIPSE, developed by the Cancer Research UK TRACERx team at UCL and the Francis Crick Institute, uses a standardized algorithm that helps resolve tumor tissue-based sample bias. Coupling Invitae’s PCM assay with ECLIPSE, the researchers analyzed 972 longitudinal plasma samples from 136 TNM I-III NSCLC patients in TRACERx who had undergone multiregion whole exome sequencing of primary tumor and relapse tissue and had 364 surveillance scans. Seventy-five of these patients experienced a recurrence of their surgically resected disease.

The researchers concluded that multiplex-anchored PCR with trinucleotide specific background models improves NSCLC relapse detection compared to standard of care clinical follow up. Using ECLIPSE, plasma samples of less than 1% purity can be used to accurately profile the clonal structure of tumors at diagnosis, during treatment and at relapse, which impacts patient outcome and has the potential to guide personalized medicine.

"Determining the best treatment plan for a cancer patient depends on several factors, including the results of current disease monitoring. Unfortunately, traditional monitoring methods such as imaging and tissue biopsy are insensitive when it comes to adequately representing a tumor or detecting relapse early in a patient’s treatment cycle," said Robert Nussbaum, M.D., chief medical officer of Invitae. "These findings further validate the role of PCM in determining a therapy’s effectiveness and identifying relapses more quickly, both of which are essential to optimizing personalized treatment plans."

PCM and other liquid biopsy approaches for monitoring MRD have the potential to become a mainstay in personalized oncology. PCM could be applied in a variety of ways to help improve patient care and prolong survival outcomes, including monitoring for recurrence, monitoring a patient’s response to therapy to inform treatment decisions, and improving clinical trial designs to help get new therapies to market sooner.

About TRACERx Study

TRACERx (Tracking Cancer Evolution through therapy (Rx)) lung study is the single biggest investment in lung cancer research by Cancer Research UK. Taking place over nine years, we believe the translational research programme is the first study to look at the evolution of cancer in real time and immense detail. Researchers follow patients with lung cancer all the way from diagnosis through to either disease relapse or cure after surgery, tracking and analysing how their cancer develops. TRACERx is led by UCL (University College London) via the Cancer Research UK Lung Cancer Centre of Excellence and also supported by the National Institute for Health Research, University College London Hospitals Biomedical Research Centre, Francis Crick Institute and the Rosetrees Trust.