On August 27, 2021 Aileron Therapeutics (Nasdaq: ALRN), a chemoprotection oncology company focused on fundamentally transforming the experience of chemotherapy for cancer patients, reported a poster presentation showcasing initial findings from its ongoing study of ALRN-6924 in healthy volunteers at the International Society for Experimental Hematology (ISEH) 50th Annual Scientific Meeting, which is currently underway (Press release, Aileron Therapeutics, AUG 27, 2021, View Source [SID1234586958]). The initial findings demonstrated that a 0.3 mg/kg dose of ALRN-6924 has been very well tolerated and resulted in p53-mediated induction of the cell cycle inhibitor p21 in healthy, normal bone marrow cells without concurrent induction of apoptosis. The poster can be viewed on Aileron’s website here.

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"We’re pleased to present our first human data demonstrating ALRN-6924’s mechanism of action, namely, p53-mediated induction of p21 in healthy, normal cells without concurrently inducing apoptosis," said Manuel Aivado, M.D., Ph.D., President and Chief Executive Officer of Aileron. "We believe these data validate our previously presented preclinical mechanism of action results for ALRN-6924 and also support the robust chemoprotective effect ALRN-6924 demonstrated against multiple chemotherapy-induced bone marrow toxicities in our Phase 1b trial in patients with p53-mutated small-cell lung cancer (SCLC). We look forward to presenting additional data from the ongoing healthy volunteer study in the future and evaluating clinical translation of these findings in our ongoing randomized, double-blind, placebo-controlled trial of ALRN-6924 in patients with p53-mutated NSCLC."

The healthy volunteer study is designed to characterize the time to onset, magnitude and duration of p21-induced cell cycle arrest in human bone marrow relative to ALRN-6924 administration. The ultimate aim of the study is to develop a universal dosing regimen for ALRN-6924 for use as a selective chemoprotective agent across a range of chemotherapies and p53-mutant tumor indications.

Aileron is currently evaluating ALRN-6924 in a Phase 1b randomized, double-blind, placebo-controlled trial of ALRN-6924 in patients with advanced p53-mutated NSCLC undergoing treatment with first-line carboplatin plus pemetrexed with or without immune checkpoint inhibitors.

In October 2020, Aileron presented data from its now completed Phase 1b clinical trial of ALRN-6924 in SCLC, demonstrating clinical proof-of-concept that treatment with ALRN-6924 resulted in a protective effect against neutropenia, thrombocytopenia and anemia in patients with p53-mutated SCLC treated with topotecan. Aileron will present final data from the Phase 1b SCLC trial and additional data from the healthy volunteer study at the upcoming European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress, being held September 16-21, 2021.

On August 27, 2021 Nordic Nanovector ASA (OSE: NANOV) reported its results for the second quarter and first half 2021 (Press release, Nordic Nanovector, AUG 27, 2021, View Source [SID1234586974]). A presentation by Nordic Nanovector’s senior management team will be webcasted live today beginning at 8:30am CEST. The webcast can be accessed from www.nordicnanovector.com in the section: Investors & Media and a recording will also be available on this page after the event.

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The results report and the presentation are available on the company’s website in the section: Investors & Media/Reports and Presentation/Interim Reports/2021.

Malene Brondberg, interim CEO of Nordic Nanovector, said: "Nordic Nanovector continues to make important progress towards completing patient enrolment into the pivotal PARADIGME trial despite ongoing disruption from the COVID-19 pandemic. This disruption has reduced the acceleration in recruitment that we anticipated as a result of the amendments we made to the trial protocol and the multiple recruitment initiatives we have implemented. We now expect to report the preliminary readout from PARADIGME in H1’2022 and are focused on delivering this crucial milestone. The Company remains convinced that Betalutin is uniquely positioned to meet the need for a chemo-free, effective yet tolerable treatment for NHL patients, coupled with its convenient administration schedule, with potential quality of life advantages for elderly and frail patients."

Operational Highlights

PARADIGME timelines revised following review of patient recruitment rate and expected impact of continuing COVID-19 pandemic caused by the spread of the more infectious SARS-CoV-2 delta variant
Preliminary three-month data readout now expected during H1’2022
94 of a targeted 120 patients have been enrolled into PARADIGME as of 26 August 2021 (83 patients enrolled as of 25 May 2021)
Successful Private Placement and oversubscribed Repair Offering completed in February and April, respectively, raised approximately NOK 422 million (USD 49.7 million) in gross proceeds
Extends the company’s cash runway into H2’2022
Promising Phase 1b data reported from the Phase 1 Archer-1 study evaluating Betalutin in combination with rituximab in 2L follicular lymphoma (FL)
The combination showed a very good safety profile comparable to that of single agent Betalutin, and early signs of efficacy, with all seven patients responding to treatment, with 6 out of 7 patients still in remission
On 3 August 2021, the Company announced that the findings from Archer-1 will be important to inform the future development strategy for Betalutin in 2L FL and that it will invest no further funds in Archer-1.
Betalutin was found to be well tolerated, with a good safety profile consistent with all previous studies, in the LYMRIT 37-05 Phase 1 trial in Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL)
Clinical activity of Betalutin was seen in the six evaluable patients receiving the highest dosing regimen
Next steps for development of Betalutin in DLBCL are under consideration
The Company has committed to hosting an R&D Day in Q4’2021 to discuss the positioning and next steps for Betalutin development and commercialisation, as well as further pipeline opportunities
Malene Brondberg was appointed interim Chief Executive Officer in July
Ms Brondberg replaces Peter Braun, who left Nordic Nanovector for personal reasons. Ms Brondberg will continue in her role as CFO. The Board has initiated a search for a new CEO
Board changes
Hilde Hermansen Steineger, PhD, decided not to stand for re-election at the AGM on 28 April 2021
Solveig Hellebust, PhD, was appointed Non-executive Director at the AGM
Financial Highlights

(Figures in brackets = same period 2020 unless otherwise stated)

Revenues for the second quarter 2021 amounted to NOK 0.0 million (NOK 0.0 million)
Total operating expenses for the second quarter 2021 were NOK 103.9 million (NOK 113.4 million)
Comprehensive loss for the second quarter 2021 amounted to NOK 101.8 million (loss of NOK 125.6 million)
Revenues for the first half 2021 amounted to NOK 0.0 million (NOK 0.0 million)
Total operating expenses for the first half 2021 decreased to NOK 205.1 million (NOK 239.3 million)
Comprehensive loss for the first half 2021 was NOK 204.0 (NOK 217.2 million)
Cash and cash equivalents amounted to NOK 450.1 million at the end of June 2021, compared to NOK 497.9 million at the end of March 2021, and NOK 294.0 million at the end of December 2020
Outlook

Nordic Nanovector’s current focus is to complete patient enrolment into PARADIGME and is targeting the readout of preliminary three-month top line data during H1’2022.

The company’s current cash position will support its operations into H2’2022 and will enable further preparatory work on the potential Betalutin BLA filing and planning for commercialisation to be undertaken.

The company believes that, if positive, the PARADIGME trial data could represent a significant value inflection point for the company and its shareholders, confirming Betalutin as a highly promising new targeted radioimmunotherapy that can address the unmet needs of R/R FL patients.

The company intends to discuss the development plan and opportunities for expanding the market for Betalutin into other NHL indications, together with other potential areas for pipeline expansion based on CD37-targeting immunotherapies, at its R&D Day, which is planned to take place in Q4’2021.

On August 27, 2021 Carina Biotech reported that has entered a collaboration agreement with Melbourne biotech AdAlta to develop precision engineered, i-body enabled CAR-T therapies that provide new hope for patients with cancer (Press release, Carina Biotech, AUG 27, 2021, View Source [SID1234586959]).

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This is a collaboration at the cutting-edge of cancer medicine, bringing together Carina’s world-leading proprietary CAR-T technologies with AdAdlta’s unique i-body platform. The agreement will develop i-body enabled CAR-T cancer immunotherapies against up to five solid tumour antigen targets.

The small size and unique targeting of i-bodies provides for greater flexibility and design options for CAR-T cells, which are ideally suited for the production of bi-specific CAR-T cells.

Bi-specific CAR-T cells have the potential to deliver precisions to difficult-to-target cancers – by targeting two antigens on cancer cells, reducing the opportunity for tumour cells to be missed, and reducing the chances of damaging healthy tissue.

Carina’s CEO, Dr Deborah Rathjen, commented: "This collaboration with AdAlta gives us the capability to generate bi-specific CAR molecules and then next-generation CAR-T cell products with enhanced cancer targeting and efficacy – something we are very excited about. The collaboration is off to a great start with Carina already having successfully inserted an AdAlta i-body into a CAR-T cell with functional cancer killing capability."

Carina and AdAlta will jointly fund pre-clinical proof-of-concept studies in mouse tumour models and will jointly own products emerging from the collaboration.

On August 27, 2021 TILT Biotherapeutics, a clinical-stage biotechnology company developing cancer immunotherapeutics, reported that new preclinical data relating to the use of its oncolytic immunotherapy platform for expressing a human IL-2 variant protein has been published in Frontiers in Immunology (1) (Press release, TILT Biotherapeutics, AUG 27, 2021, View Source [SID1234586975]). The paper was independently authored by researchers at the University of Helsinki (Finland) and other leading institutions, together with TILT Biotherapeutics.

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The paper, entitled: "Oncolytic Adenovirus Coding for a Variant Interleukin 2 (vIL-2) Cytokine Re-Programs the Tumor Microenvironment and Confers Enhanced Tumor Control," describes a study with TILT-452 (in the paper referred to as Ad5/3-E2F-d24-vIL2), which is a novel tumor-selective oncolytic adenovirus encoding for an improved variant of IL-2. TILT-452 was used in vitro and in vivo in a model of immunosuppressive pancreatic cancer leading to substantial intratumoral immune modulation and potent antitumor responses.

TILT-452 is constructed using the same platform as TILT’s lead asset, TILT-123, which is a 5/3 chimeric serotype adenovirus armed with two human cytokines; TNF alpha and IL-2. TILT-123 has demonstrated a 100% response rate in pre-clinical cancer models in vivo, and it is currently in multiple Phase 1 clinical trials (2,3) with interim data expected later this year.

The platform (Ad5/3-E2F-d24-) features unique double tumor specificity by restricting viral replication with trans-complemented mutations and a tumor-specific promoter, with transgene expression controlled by tumor-specific virus replication, allowing local and systemic administration. Moreover, the chimeric capsid from adenovirus serotype 5 that carries a knob from serotype 3 is used for increased entry into cancer cells through desmoglein 2, which is highly expressed by most malignant cells. Another advantage of using a vectored system for the protein delivery is the prolonged and spatially restricted high production in tumor lesions with minimum leakage to healthy tissues.

TILT Biotherapeutics’ CEO, Akseli Hemminki, a biotech entrepreneur and oncologist who has personally treated 300 patients with eleven different oncolytic viruses, said, "TILT-452 is a promising candidate for translation into clinical trials in human immunosuppressive solid tumors, such as pancreatic cancer and other difficult malignancies with unmet clinical need. We continue to progress this as part of our portfolio of next generation oncolytic viruses."

The heart of TILT’s approach revolves around the use of armed oncolytic adenoviruses, using cytokines and other molecules to boost the patient’s immune response to better enable it to find and destroy cancer cells. The company is advancing its preclinical pipeline towards further clinical trials in 2023.

On August 27, 2021 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), reported the grant of patent no. ZL201580013695.X entitled "Antibody molecules to LAG-3 and uses thereof" by the Chinese Patent Office (Press release, Immutep, AUG 27, 2021, View Source [SID1234586961]).

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This new Chinese patent follows the grant of the corresponding Australian, United States, European, and Japanese patents announced in 2018 through 2020.

In particular, the claims of the patent are directed to LAG525, pharmaceutical compositions comprising LAG525, nucleic acid molecules that code for the LAG525 antibody, an expression vector or host cell that comprises the nucleic acid molecules, and to the use of LAG525 in the manufacture of a preparation for the treatment of cancer or infectious disease.

LAG525 (INN: leramilimab) is a humanised form of Immutep’s IMP701 antibody which is out-licensed to Novartis AG.

The patent is co-owned by Novartis AG and Immutep S.A.S. and will expire on 13 March 2035.

About IMP701 and LAG525

IMP701 is a therapeutic antagonist antibody originally developed by Immutep S.A. (now Immutep S.A.S.) to target LAG-3. This antibody plays a role in controlling the signalling pathways in both effector T cells and regulatory T cells (Treg). The antibody works by activating effector T cells by blocking inhibitory signals that would otherwise switch them off, and also by inhibiting Treg function that normally prevents T cells from responding to antigen stimulation. The antibody therefore removes two brakes that prevent the immune system from responding to and killing cancer cells. In contrast, some other antagonist LAG-3 antibodies in development target only the effector T cell pathway and don’t address the Treg pathway.

LAG525, a humanised form of IMP701, is being evaluated in several Phase I and/or Phase II clinical trials in combination with Novartis’ PD1 inhibitor spartalizumab for the treatment of various cancers. Novartis has full responsibility for the continued development of the antibody program and Immutep is eligible to receive development-based milestone payments and royalties on sales following commercialisation of the antibody.