On October 28, 2021 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a biotechnology company developing novel LAG-3 related immunotherapy treatments for cancer and autoimmune disease, reported an update on the ongoing development of its product candidates, eftilagimod alpha ("efti") and IMP761 for the quarter ended 30 September 2021 (Press release, Immutep, OCT 28, 2021, View Source [SID1234592105]).

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Efti Development Program for Cancer

AIPAC – Phase IIb clinical trial – ongoing
Immutep will report final Overall Survival (OS) data from its Phase IIb AIPAC clinical trial evaluating efti in metastatic breast cancer as a late breaker poster at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting 2021 taking place in the US and virtually from 10-14 November.

Immutep previously reported initial OS data from approximately 60% of events in December 2020 at the San Antonio Breast Cancer Symposium. The study reported a promising and improving trend in OS in the total population with a median survival benefit of +2.7 months from efti plus chemotherapy, compared to chemotherapy plus placebo. In addition, a statistically significant OS benefit was observed in the efti group in key pre-defined patient groups, including patients under 65 years of age and those with low starting monocyte count.

AIPAC-003 – Phase III – new
Immutep is continuing the preparation and planning steps for its Phase III clinical trial evaluating efti in patients with metastatic breast cancer.

TACTI-003 – Phase IIb clinical trial – new
In July 2021, Immutep completed all the necessary competent authority steps with the US Food and Drug Administration (FDA) and has received institutional review board approval to commence its Phase IIb TACTI-003 trial in the US. Recruitment has also opened in the Ukraine and more sites and countries will be added in the coming months. This follows the receipt of Fast Track designation in 1st line recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) from the US FDA in April 2021.

In addition, Immutep will be presenting the trial design for TACTI-003 via a poster at the SITC (Free SITC Whitepaper) 2021 conference in November.

TACTI-002 (also designated KEYNOTE-PN798) – Phase II clinical trial – ongoing
In September 2021, Immutep enrolled the last patient into Stage 2 of Part B of the Phase II TACTI-002 study, completing recruitment of 2nd line PD-1/PD-L1 refractory non-small cell lung cancer (NSCLC) patients into the trial. Recruitment is continuing for the additional 74 1st line NSCLC patients for the expansion of Part A, with 70 patients already enrolled. Recruitment for the expansion of Part A of the study continues to be ahead of the expected recruitment rate.

Immutep reported favourable interim Overall Response Rates (ORR) together with encouraging duration and depth of response in 1st line NSCLC (Part A) and 2nd line HNSCC (Part C) at ASCO (Free ASCO Whitepaper) in June 2021. The Company will report data from Part C of TACTI-002 at the SITC (Free SITC Whitepaper) 2021 conference in November. Additional data from this study trial are planned to be reported in the first half of calendar year 2022.

INSIGHT
INSIGHT is an investigator-initiated Phase I trial at the Institute of Clinical Cancer Research, Krankenhaus Nordwest (IKF) investigating different combination treatments with efti and a different route of administration for efti. INSIGHT consists of 5 different arms from stratums A to E.

INSIGHT-003 – triple combination
In August 2021, the first patient was enrolled and safely dosed in INSIGHT-003, also referred to as stratum C of INSIGHT. Patient recruitment is ongoing with 4 out of a total of 20 patients with various solid tumours now participating in the trial. First interim results are expected to be reported in 2022.

INSIGHT-004 – combination with avelumab
Results from INSIGHT-004 were presented at the ESMO (Free ESMO Whitepaper) Congress 2021 held 16-21 September. The results are in line with the previous poster presentation at ASCO (Free ASCO Whitepaper) 2021.

INSIGHT-005 – combination with bintrafusp alpha
INSIGHT-005, known as stratum E of INSIGHT, will involve 12 patients with solid tumours and will evaluate efti in combination with bintrafusp alfa. It will be conducted under Immutep’s collaboration agreement with Merck KGaA, Darmstadt, Germany.

Separately to Immutep’s ongoing collaboration agreement with Merck KGaA, Merck KGaA and GlaxoSmithKline announced a mutual decision to terminate their agreement to co-develop bintrafusp alfa. Accordingly, Immutep and Merck KGaA are working closely to determine the next steps for the INSIGHT-005 study.

EAT COVID – Phase II clinical trial – ongoing
The investigator-initiated EAT COVID study is continuing at the University Hospital Pilsen in the Czech Republic. Patient recruitment into the trial by the hospital has been slower than anticipated due to a significant decline in the number of infections and improving vaccination rates in the Czech Republic. The Company will provide an update on the trial in due course.

IMP761 Development Program for Autoimmune Disease

During the quarter, Immutep continued GMP manufacturing preparations for IMP761 and is planning for toxicology studies and other pre-clinical evaluations of this promising candidate.

Partnerships

EOC Pharma
Immutep’s Chinese partner for efti, EOC Pharma, announced it plans to expand its clinical trial pipeline for efti (designated EOC202 in China) in China. EOC is preparing to initiate a clinical study of efti in combination with an anti-PD-1 therapy in the first half of calendar year 2022. This new trial builds on EOC’s previously announced Phase II trial evaluating efti in combination with chemotherapy in metastatic breast cancer patients.

Novartis
Immutep’s partner, Novartis presented two posters at the ESMO (Free ESMO Whitepaper) Congress 2021. One poster included data from its PLATForM Phase II study of novel spartalizumab combinations in melanoma, concluding patients with LAG-3+ melanoma may be more likely to respond to spartalizumab + ieramilimab (LAG525) treatment.

Novartis also presented data from its Phase II, open-label, 3-arm study, in patients with advanced triple-negative breast cancer regardless of PD-L1 status progressing after adjuvant or one prior line of systemic therapy for metastatic disease, but who had not received an immune checkpoint inhibitor. Patients were randomised 1:1:1 to LAG525 + spartalizumab, LAG525 + spartalizumab + carboplatin, or LAG525 + carboplatin. As no arms of the study met the proof of preliminary efficacy criteria, no further investigation is planned for this study.

LAG525 is a humanised anti-LAG-3 antibody derived from Immutep’s IMP701 antibody, which is out-licensed to Novartis.

Intellectual Property

Immutep was granted three new patents relating to the protection of LAG525 (IMP701), which is fully out-licensed to Novartis, by the Chinese Patent Office, the Indian Patent Office and the Malaysian patent office during the quarter. The patents are co-owned by Novartis AG and Immutep SAS and follow the grant of the corresponding Australian, United States, European, and Japanese patents announced in 2018 through 2020.

Financial Summary – Q1 FY221

Cash receipts from customers for the quarter was $56k, compared to $10k in Q4 of FY21 (i.e. the quarter ended 30 June 2021).

The net cash used in G&A activities in the quarter was $1.01 million compared to $409k in Q4 FY21. The increase compared with last quarter is mainly due to capital raising related costs that were expensed in July 2021. Payments to Related Parties, detailed in Item 6 of the Appendix 4C cash flow report for the quarter includes $135k in payment of Non-Executive Director’s fees and Executive Director’s salary.

The net cash used in Research and Development activities in the quarter was $6.83 million, compared to $5.45 million in Q4 FY21. The significant increase is mainly due to increased clinical trial and manufacturing activities. Total net cash outflows used in operating activities in the quarter was $5.37 million. In comparison, total net cash outflows from operating activities in Q4 FY21 was $5.71 million.

Immutep received a €2,126,617 (~$3.42 million) research and development (R&D) tax incentive payment in cash from the French Government under its Crédit d’Impôt Recherche scheme (CIR) during the quarter in respect of expenditure incurred during calendar year 2020 on eligible R&D activities conducted in the European Union.

As part of the Company’s two-tranche financing announced in June 2021, shareholders approved the second tranche of an institutional placement of shares at the Company’s Extraordinary General Meeting in July 2021. The second tranche of the institutional placement raised $46.3 million. In total, Immutep raised $60 million via the institutional placement, which was supported by multiple institutional investors in Australia and offshore.

A further $7.2 million was raised from a Share Purchase Plan (SPP) completed in July 2021, which enabled existing eligible shareholders to participate in the financing on the same terms as the institutional placement. Due to strong demand from eligible shareholders, the amount raised exceeded the targeted amount sought to be raised ($5 million) under the SPP.

The Company’s cash and cash equivalent balance as at 30 September 2021 was $106.39 million compared to a balance of $60.59 million as at 30 June 2021. The enhanced cash balance puts the company in a strong financial position with an estimated cash reach of December 2023.

A copy of the Appendix 4C – Quarterly Cash Flow Report for the quarter is attached.

On October 28, 2021 Triumvira Immunologics ("Triumvira"), a clinical-stage company developing novel, targeted autologous and allogeneic T cell therapeutics that co-opt the natural biology of T cells to treat patients with solid tumors, reported that it has appointed Deyaa Adib, M.D., to serve as the company’s Chief Medical Officer, effective immediately (Press release, Triumvira Immunologics, OCT 28, 2021, View Source [SID1234592121]). Dr. Adib will report to President and CEO Dr. Paul Lammers and will succeed Dr. Sabine Chlosta.

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As a seasoned industry leader, Dr. Adib has over 24 years of medical oncology experience in the biotechnology and pharmaceutical industries, including seven successful registrations across solid tumor and hematologic malignancy indications. He previously served as acting chief medical officer at Rain Therapeutics, where he built the oncology portfolio leading to a successful IPO, and vice president of late-stage development at Blueprint Medicines advancing the development of avapritinib approved for gastrointestinal stromal tumor and advanced systemic mastocytosis. Dr. Adib also served as global therapeutics head for solid tumors at Baxalta, advancing the development of imalumab in colorectal cancer, non-small cell lung cancer (NSCLC), and ovarian cancer, and licensing nanoliposomal irinotecan that was subsequently approved for pancreatic cancer. In this role, he also led the efforts to secure licensing and development of a CD-19 target with Precision Biosciences in B cell malignancies and PD1, LAG3, TIM3 solid tumor targets with Symphogen, a Servier company. He also served as head of hematologic malignancies at ARIAD Pharmaceuticals (now part of Takeda) leading the global clinical program for ponatinib dose-finding and line extension in chronic myeloid leukemia.

On October 28, 2021 Synthekine Inc., an engineered cytokine therapeutics company, reported it is advancing its IL-2 partial agonist, STK-012, into clinical investigation following clearance of its investigational new drug (IND) application by the U.S. Food and Drug Administration (FDA) (Press release, Synthekine, OCT 28, 2021, View Source [SID1234592138]).

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Synthekine will evaluate STK-012 in a Phase 1a/1b, open-label, multi-center, dose escalation study. The study will investigate STK-012 both as a monotherapy and in combination with an immune checkpoint inhibitor in individuals with advanced solid tumors.

"IL-2 is a cytokine with proven benefit as an anti-cancer therapy. However, the indiscriminate activity of IL-2 can cause severe toxicities, limiting its clinical application," said Naiyer Rizvi, M.D., chief medical officer of Synthekine. "We have designed STK-012 to uncouple the efficacy and toxicity of IL-2, and we look forward to now investigating its potential in our first clinical development program."

STK-012 is designed as an alpha/beta-biased IL-2 partial agonist to selectively stimulate antigen-activated T cells, which are associated with potent anti-tumor activity, and avoid stimulation of toxicity causing immune cells, such as natural killer cells. Synthekine has presented data at AACR (Free AACR Whitepaper) 2021 from preclinical studies demonstrating a mouse surrogate of STK-012 achieved superior tumor regression compared to both wild-type mouse IL-2 and a non-alpha-IL-2 agent, representing a different approach to biasing IL-2. In toxicity models, the mouse surrogate of STK-012, unlike these same comparators, was well tolerated and did not induce capillary leak syndrome (CLS), a dose-limiting IL-2-related toxicity which can result in death. In non-human primate models, STK-012 demonstrated a significantly improved pharmacokinetic and toxicity profile versus both aldesleukin (a recombinant IL-2 therapy) and a non-alpha-IL-2 agent.

On October 28, 2021 HanAll Biopharma (KRX: 009420.KS) reported that the company had achieved sales of 25.5 billion won, an operating profit of 2.2 billion won, and a net profit of 2.1 billion won in the third quarter of 2021 (Press release, HanAll Biopharma, OCT 28, 2021, View Source [SID1234592154]).

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In the first nine months of the year, net sales were 76.7 billion won, a 15% increase compared to the same period last year, and the operating profit increased by 67% to 9.2 billion won. Increased sales were largely due to strong revenues with double digit growth from major products such as Normix, an antibiotic for gastrointesinal infection; Eligard, a prostate cancer treatment; and Biotop, a probiotic product.

As of the end of the third quarter, HanAll Biopharma maintained a stable financial status with net cash of 87.6 billion won and reported assets of 203.0 billion won, an equity of 163.9 billion won, and liabilities of 39.1 billion won.

[R&D Pipeline]

– HL161 (a novel, fully human, subcutaneous anti-FcRn antibody therapeutic for autoimmune diseases)
HL161 (INN: batoclimab), an antibody drug for autoimmune diseases caused by pathogenic antibodies, is currently undergoing clinical trials in the US and China through HanAll’s partners, Immunovant and Harbor BioMed.

The licensed partner in the US and Europe, Immunovant, is preparing to resume clinical trials, which were put on hold in February of this year due to an issue related to increased cholesterol. Program-wide data review suggests that HL161 has a broader therapeutic window than previously anticipated and that lipid elevations are predictable, manageable, and appear to be driven by reductions in albumin. Immunovant announced its plan

1) to return to the clinic and initiate a pivotal Phase 3 myasthenia gravis (MG) trial and Phase 2 in warm autoimmune hemolytic anemia (WAIHA) in the first half of 2022 following meetings with regulators including the FDA,
2) to communicate with the FDA and other authorities to discuss future plans for Phase 2 trials for thyroid eye disease or other thyroid related disease and
3) to initiate new studies in two additional indications in 2022.

The licensed partner in greater China, Harbour BioMed, is currently conducting clinical trials in myasthenia gravis (MG), immune thrombocytopenia (ITP), neuromyelitis optica (NMO), and thyroid eye disease (TED) in China. In September, Harbour BioMed released that the China National Medical Products Administration (NMPA) has approved the Investigational New Drug (IND) application to initiate a Phase 2 trial of batoclimab in patients with chronic inflammatory demyelinating polyneuropathy (CIDP).

Harbor BioMed reported the first dosing of the first patient in registrational Phase 3 trial of batoclimab in myasthenia gravis in China in September and expects BLA submission for the disease next year.

In Japan, HanAll Biopharma is preparing a Phase 3 trial for myasthenia gravis (MG) in collaboration with Immunovant. The study is expected to start in 2022.

– HL036 (a novel, topical anti-TNF biologic therapy for dry eye disease)
HL036 (INN: tanfanercept), jointly developed by HanAll Biopharma and Daewoong Pharmaceutical, is a novel biologic treatment under development to treat inflammatory eye diseases by inhibiting TNF, which is involved in ocular inflammation. The first Phase 3 clinical trial (VELOS-2) for dry eye disease was completed last year.

HanAll submitted the IND for the second Phase 3 clinical trial (study name: VELOS-3) to the US FDA on July 22, and is expected to begin clinical trials in the fourth quarter this year and have topline results next year. Due to the recent COVID related delays of global transportation, there was a delay in the investigational drug transportation. Accordingly clinical study initiation was rescheduled from the third quarter to the fourth quarter.

The VELOS-3 study is a Phase 3, multicenter, randomized, double-blind, and placebo-controlled study evaluating the efficacy and safety of tanfanercept ophthalmic solution 0.25% compared to placebo in subjects with dry eye disease.

Harbor BioMed, the license holder for the Chinese market, started a pivotal Phase 3 trial in dry eye disease in the first half of the year, and plans to file a biologics license application (BLA) with NMPA in 2022 after the study ends.

– HL189 (tanfanercept)
HanAll Biopharma is exploring the options to expand the indications of tanfanercept to new inflammatory eye disorders including uveitis. Preclinical studies on uveitis have been conducted. The company will decide on new indications development plan in 2022.

– HL186/HL187 (novel immune-oncology therapies)
HL186 and HL187 projects are novel immuno-oncology antibodies that target TIM-3 and TIGIT, respectively, developed in collaboration with Daewoong Pharmaceutical. Both programs are at preclinical stage. The companies aim to develop differentiated immune checkpoint inhibitors with better efficacy and higher response rates for patients with cancer.

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