On March 30, 2020 Bayer reported that Nubeqa (darolutamide) receives EU approval as a new treatment for men with non-metastatic castration-resistant prostate cancer (Press release, Bayer, MAR 30, 2020, View Source [SID1234555995]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The European Commission has granted marketing authorisation in the European Union (EU) for Nubeqa (darolutamide), an oral androgen receptor inhibitor (ARi). The approval is based on Phase III ARAMIS trial results showing a statistically significant improvement in metastasis-free survival (MFS) for darolutamide plus androgen deprivation therapy (ADT) versus placebo plus ADT, and a favorable safety profile.

The compound, which is developed jointly by Orion Corporation and Bayer, is indicated for the treatment of men with non-metastatic castration-resistant prostate cancer (nmCRPC), who are at high risk of developing metastatic disease. Bayer is responsible for global commercialisation of darolutamide, with a co-promotion of Bayer and Orion in certain European markets, e.g. France, Germany, Italy, Spain, the UK, Scandinavia and Finland.

Nubeqa has a distinct chemical structure which inhibits the growth of prostate cancer cells while limiting the burden of side effects on patients’ everyday lives. The EU approval is based on the pivotal Phase III ARAMIS trial data evaluating the efficacy and safety of darolutamide plus androgen deprivation therapy (ADT) compared to placebo plus ADT. Results demonstrated a highly significant improvement in the primary efficacy endpoint of metastasis-free survival (MFS) of darolutamide plus ADT, with a median of 40.4 months, versus 18.4 months for placebo plus ADT (p<0.001), and a favorable safety profile. Nubeqa is already approved in the U.S., Australia, Brazil, Canada, as well as Japan and filings in other regions are underway or planned by Bayer.

"As men with nmCRPC typically have no symptoms and are leading active lives, it is important to have treatment options that delay the progression of their cancer while minimising the burdensome side effects of treatment, allowing them to maintain their lifestyle with little disruption. Darolutamide provides a welcome new option with a favorable safety profile that helps patients to stay on therapy and allows us to meet these treatment goals," said Karim Fizazi, M.D., Ph.D., Professor of Medicine at the Institut Gustave Roussy, Villejuif, France.

Prostate cancer that is confined to the prostate region and is treated with ADT but keeps progressing, even when the amount of testosterone is reduced to very low levels in the body, is known as nmCRPC. In Europe over 67,000 men are estimated to have a CRPC diagnosis, based on 2018 prostate cancer incidence numbers. About one-third of men with nmCRPC go on to develop metastases within two years.

"We are pleased to collaborate with Bayer in combining our expertise in the development of Nubeqa and look forward to our co-promotion in Europe to support patients with non-metastatic castration-resistant prostate cancer and their healthcare professionals", said Satu Ahomäki, Senior Vice President, Commercial Operations of Orion Corporation.

"The approval of Nubeqa in Europe supports our commitment to delivering innovative medicines that are differentiated from current options and that address unmet medical needs, improve treatment outcomes and maintain quality of life for men at all stages of the prostate cancer continuum," said Robert LaCaze, Member of the Executive Committee of Bayer’s Pharmaceuticals Division and Head of the Oncology Strategic Business Unit. "We expect to report results from the pre-planned OS analysis at an oncology meeting later this year."

In the ARAMIS trial, overall survival (OS) and time to pain progression were additional secondary efficacy endpoints. At the time of final MFS analysis, a positive trend in OS was observed; OS data were not yet mature. Results from the pre-planned final OS analysis are expected to be presented at an upcoming scientific meeting in 2020. The MFS result was additionally supported by a delay in time to pain progression as compared to placebo plus ADT. All other secondary endpoints, time to cytotoxic chemotherapy, and time to a symptomatic skeletal event (SSE), also demonstrated a benefit in favor of darolutamide at the time of final MFS analysis.

Darolutamide plus ADT has demonstrated a favorable safety profile. The most frequent adverse reactions in the darolutamide plus ADT arm, that occurred with an absolute increase in frequency of ≥2% compared to placebo plus ADT, were fatigue/asthenic conditions (16% vs. 11%), pain in extremity (6% vs. 3%), and rash (3% vs. 1%). Discontinuation due to adverse events occurred in 9% of patients in both arms of the study.

About the ARAMIS trial
The ARAMIS trial is a randomized, Phase III, multi-center, double-blind, placebo-controlled trial evaluating the safety and efficacy of oral darolutamide in patients with nmCRPC who are currently being treated with ADT and are at high risk for developing metastatic disease. In the clinical study, 1,509 patients were randomized in a 2:1 ratio to receive 600 mg of darolutamide orally twice daily or placebo along with ADT. Patients with a history of seizure were allowed in the study.

About Nubeqa (darolutamide)
Darolutamide was approved in March 2020 in the European Union under the brand name Nubeqa for the treatment of men with non-metastatic castration-resistant prostate cancer (nmCRPC), who are at high risk of developing metastatic disease. Nubeqa has also received regulatory approval in the U.S., Australia, Brazil, Canada as well as Japan, and filings in other regions are underway or planned by Bayer.

Nubeqa is an oral androgen receptor inhibitor (ARi) with a distinct chemical structure that binds to the receptor with high affinity and exhibits strong antagonistic activity, thereby inhibiting the receptor function and the growth of prostate cancer cells. Darolutamide is also being investigated in a Phase III study in metastatic hormone-sensitive prostate cancer (ARASENS trial). Information about these trials can be found at www.clinicaltrials.gov.

About castration-resistant prostate cancer (CRPC)
Prostate cancer is the second most commonly diagnosed malignancy in men worldwide. In 2018, an estimated 1.2 million men were diagnosed with prostate cancer, and about 358,000 died from the disease worldwide. Prostate cancer is the fifth leading cause of death from cancer in men. Prostate cancer results from the abnormal proliferation of cells within the prostate gland, which is part of a man’s reproductive system. It mainly affects men over the age of 50, and the risk increases with age.

Treatment options range from surgery to radiation treatment to therapy using hormone-receptor antagonists, i.e., substances that stop the formation of testosterone or prevent its effect at the target location. However, in nearly all cases, the cancer eventually becomes resistant to conventional hormone therapy.

CRPC is an advanced form of the disease where the cancer keeps progressing despite ADT treatment, even when the amount of testosterone is reduced to very low levels in the body. In men with progressive nmCRPC, a rapid prostate specific antigen (PSA) doubling time has been consistently associated with reduced time to first metastasis and death.

On March 30, 2020 AC Immune SA (NASDAQ: ACIU), a Swiss-based, clinical-stage biopharmaceutical company with a broad pipeline focused on neurodegenerative diseases, reported financial results for the year ended December 31, 2019, and provided a business and 2020 research and development outlook (Press release, AC Immune, MAR 30, 2020, View Source [SID1234555994]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Prof. Andrea Pfeifer, CEO of AC Immune SA, commented: "AC Immune is building on clinical and business accomplishments in 2019, and anticipates multiple clinical, value-creating milestones in 2020. We anticipate reporting data from two studies of our proprietary anti-Abeta vaccine program, ACI-24 as well as Phase 1 results for the small molecule Morphomer Tau aggregation inhibitor, ACI-3024, in partnership with Eli Lilly and Company.

Prof. Pfeifer continued: "In parallel, our heritage as a leader in delivering cutting-edge science enables our Company to advance novel preclinical therapeutic and diagnostic candidates focused on emerging targets and neuroinflammation towards the clinic, setting the stage for additional value creation and partnership opportunities. AC Immune’s leading position in the field is built upon our proprietary discovery technology platforms, SupraAntigenTM and MorphomerTM, as well as our personalized medicine approach and exceptional development execution."

2019 and Q1 2020 Research & Development Highlights

Successful execution in preclinical and clinical development during 2019 resulted in a stronger pipeline.

§A Phase 1 study is ongoing for ACI-3024, a first-in-class investigational oral small molecule Morphomer Tau specific aggregation inhibitor that will be studied in neurodegenerative diseases characterized by the presence of pathological Tau aggregates. The initial CHF 60 million milestone payment has been modified such that Lilly has paid AC Immune CHF 30

million during Q3 2019 and CHF 10 million in Q1 2020; and, AC Immune now is eligible for a new additional milestone payment of CHF 60 million within 60 days after dosing of the first patient in the first Phase 2 clinical trial of a Morphomer Tau in the United States or European Union. The amendment to the financial terms increases the total deal value by CHF 40 million to CHF 1.86 billion, up from CHF 1.82 billion.

§Initiation of a second Phase 2 trial of semorinemab in patients with moderate AD, by our collaboration partner Genentech, a member of the Roche Group. This antibody is also being studied in a separate Phase 2 trial in prodromal to mild AD

§Received a milestone payment from our collaboration partner, Life Molecular Imaging, in connection with the initiation of a Phase 2 study in AD of the Tau positron emission tomography (PET) tracer PI-2620

§Initiation of a Phase 1b/2a clinical trial in early AD to evaluate the anti-phospho-Tau vaccine, ACI-35.030, which targets pathological Tau and is intended as a disease-modifying treatment for AD and other Tauopathies in collaboration with Janssen Pharmaceuticals, Inc

§Initiation of a substudy by our partner Genentech, a member of the Roche Group, within the ongoing Phase 2 Alzheimer’s Prevention Initiative (API) trial of AC Immune’s investigational candidate, crenezumab. This substudy aims to measure Tau burden using PET in order to increase the understanding of disease progression in the preclinical stage of autosomal dominantly inherited AD

§Presented initial interim data from an on-going Phase 1b trial of the ACI-24 anti-Abeta vaccine to treat Down syndrome (DS)-related AD

§Discontinuation by our collaboration partner Roche of the CREAD and CREAD 2 Phase 3 studies of the anti-beta-amyloid antibody, crenezumab, in people with prodromal to mild sporadic AD

§Established a research collaboration with leading scientists at the Perelman School of Medicine, University of Pennsylvania focused on studying the pathological mechanisms of TDP-43 misfolding and aggregation

§Awarded a new grant from The Michael J. Fox Foundation (MJFF) for development of AC Immune’s pioneering alpha-synuclein PET tracers

§Hosted two Key Opinion Leader (KOL) events focused on "untangling" Tau pathology as an important therapeutic and diagnostic target for AD and other neurodegenerative diseases, and on treating DS-related AD

2020 Research & Development Outlook

The coming years will be transformational for the field of neuroscience and AC Immune is poised to make significant clinical contributions, capturing substantial interest and value in 2020 and beyond. The Company will deliver multiple near-term catalysts, including results from five clinical trials. The Company’s sustained growth is driven by its industry-leading Roadmap to Successful Therapies for Neurodegenerative Diseases, and is fueled by its proprietary technology platforms, SupraAntigenTM and MorphomerTM, which continue to generate therapeutic antibody, small molecule and vaccine candidates.

2020 Clinical Readouts

§Semorinemab, anti-Tau antibody: Phase 2 trial primary completion (estimated last patient, last visit) in prodromal/mild in Q2
§ACI-24 anti-Abeta vaccine in DS: Phase 1b full study reporting in H2
§ACI-35.030 anti-pTau vaccine: Phase 1b/2a in AD interim analysis in Q2
§ACI-3024 small molecule Morphomer Tau aggregation inhibitor: Phase 1 results in healthy volunteers in Q2; data disclosed by partner in H2 (expected)
§ACI-24 in AD: Phase 2, 12-month interim analysis in H2

2020 Preclinical Milestones

§Alpha-synuclein antibody: started investigational new drug (IND)-enabling studies for lead candidate in Q1
§Anti-TDP-43 antibody: declare clinical lead and start IND-enabling studies in Q2
§ Alpha-synuclein small molecule: identify first biologically active small molecule in Q2
§Alpha-synuclein imaging agent: advance third generation candidate to clinical stage in Q4
§Neuroinflammation: declare lead candidates for small molecule and antibody programs in Q4

Prof. Pfeifer concluded: "In summary, 2020 begins a decade with the potential for major neuroscience advances. With AC Immune’s remarkably broad development pipeline focused on neurodegenerative diseases we have multiple opportunities to contribute to the advancement of this field from a business, clinical and human perspective."

Analysis of Financial Statements for the year ended December 31, 2019Cash Position: The Company had a total cash balance of CHF 288.6 million, comprised of CHF 193.6 million in cash and cash equivalents and CHF 95 million in short-term financial assets. This compares to a total cash balance of CHF 186.5 million as of December 31, 2018. The increase of CHF 102.1 million is principally due to the CHF 80 million upfront payment, USD 50 million convertible equity note and CHF 30 million milestone payment related to the agreement with Lilly. The total shareholders’ equity position increased to CHF 272.4 million from CHF 177.6 million as of the prior year. The Company’s cash balance provides enough capital resources to progress through at least Q1 2024

Revenues: Revenues for the year ended December 31, 2019 totaled CHF 111.0 million. This represents an increase of CHF 103.8 million compared to 2018. The increase for the year end relates to the recognition of CHF 75.7 million from the right-of-use license and research and development activities linked to the 2018 Lilly agreement and a CHF 30 million payment for the first milestone achieved with Lilly. Additionally, the Company recorded a EUR 2 million (CHF 2.2 million) in connection with the initiation of a Phase 2 trial in AD of Tau PET Tracer with Life Molecular Imaging
§R&D Expenditures: R&D expenses increased by CHF 6.2 million to CHF 50.4 million for the year ended December 31, 2019. Of this increase, CHF 1.7 million relates to increases in R&D expenses directly allocated to R&D programs such as a CHF 0.9 million increase related to higher research, preclinical and manufacturing costs for the lead alpha-

3 / 8

synuclein antibody and a CHF 0.7 million increase for manufacturing and preparation of the Phase 2 study for ACI-24 for DS. Additionally, the personnel costs increased by CHF 1.6 million through the addition of 16 FTEs with remaining increases of CHF 2.8 million in the area of consumables, depreciation of R&D equipment and regulatory and quality assurance

§G&A Expenses: For the year ended December 31, 2019, G&A increased CHF 3.6 million to CHF 16.1 million. Increases were driven by personnel and IT expenses
§IFRS Income/(Loss) for the period: The Company recorded net income after taxes of CHF 45.4 million for the year ended December 31, 2019, compared with net losses of CHF 50.9 million for 2018

2020 Financial Guidance

For the full year 2020, the Company expects its total cash burn to range between CHF 65‒80 million at constant exchange rates.

On March 30, 2020 Epigenomics AG (Frankfurt Prime Standard: ECX, OTCQX: EPGNY; the "Company") reported, with approval of the Supervisory Board, to increase the share capital using the Authorized Capital 2019/I. The Company’s share capital shall be increased from currently EUR 43,527,692.00 by up to EUR 3,602,154 to up to EUR 47,129,846.00 by issuing up to 3,602,154 new registered no par value shares of the Company against cash contributions (Press release, Epigenomics, MAR 30, 2020, View Source [SID1234555993]). The placement price per new share will be determined following a bookbuilding process. The new shares will be offered by way of a private placement to institutional investors with the exclusion of the shareholders’ subscription rights and carry full dividend rights as of January 1, 2019.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

M.M.Warburg & CO (AG & Co.) Kommanditgesellschaft auf Aktien is acting as sole underwriter of the transaction. The sole placement agent for the private placement in the U.S.A. is Raymond James & Associates, Inc.

On March 30, 2020 TCR2 Therapeutics Inc. (Nasdaq: TCRR), a clinical-stage immunotherapy company developing the next generation of novel T cell therapies for patients suffering from cancer, reported financial results for the fourth quarter and full year ended December 31, 2019 and provided a corporate update (Press release, TCR2 Therapeutics, MAR 30, 2020, View Source [SID1234555984]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The past twelve months represent an exciting period for TCR2 as we advanced two programs into clinical trials. Last year we began using TC-210 to treat patients with mesothelin-positive solid tumors and, more recently, we initiated a Phase 1/2 trial of TC-110 in patients with CD19-positive hematological malignancies because we believe that TRuC-T cells alone can improve on the benefit provided by approved CAR-Ts," said Garry Menzel, Ph.D., President and Chief Executive Officer of TCR2 Therapeutics. "Looking ahead, 2020 is a pivotal year for the Company with interim Phase 1 data for both TC-210 and TC-110 as well as updates on new targets, our platform enhancements and allogeneic TRuC-T cells. With a year-end 2019 cash balance of $158.1 million, we are in a strong financial position to maintain runway into 2022 and execute on our strategic priorities."

"Commercially available CD19 CAR-Ts provide durable benefit in fewer than half of patients with lymphoma and their approval in acute lymphoblastic leukemia (ALL) remains limited to pediatric patients because they result in excessive toxicity in adult patients, as I witnessed while developing Kymriah," said Alfonso Quintás Cardama, M.D., Chief Medical Officer of TCR2 Therapeutics. "Our TRuC T-cells are more effective at trafficking in solid tumor models, which lymphoma tumors resemble, and are metabolically fitter than CAR-Ts, which enhances their ability to persist longer within the immunosuppressive solid tumor microenvironment. This gives us confidence that TC-110 may be more effective in treating patients with lymphoma and could allow us to salvage those who have previously failed CD19-directed CAR-Ts. In addition, we have shown that TRuC-T cells consistently release lower levels of cytokines in preclinical experiments, which could translate into a more favorable toxicity profile that would allow us to treat adult patients with ALL more safely."

Recent Developments

The U.S. Food and Drug Administration cleared the investigational new drug (IND) application for TC-110. TCR2 initiated its Phase 1/2 trial to treat patients with CD19-positive B-cell hematological malignancies, including adult acute lymphoblastic leukemia (aALL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and other non-Hodgkin lymphoma (NHL) subtypes.

TCR2 established operational capabilities at its manufacturing facility in Stevenage, UK and expects to use the facility to manufacture and supply clinical material after approval by the UK Medicines and Healthcare Regulatory Agency (MHRA).

TCR2 presented a poster at the 2020 Keystone Symposia Conference on Emerging Cellular Therapies: Cancer and Beyond highlighting allogeneic (off-the-shelf) T Cell Receptor Fusion Constructs (TRuC) T cells that lack alloreactivity and upregulate activation markers, secrete cytokines and kill tumor cells in an antigen-specific manner.

COVID-19 has significantly impacted the global healthcare system, including the conduct of clinical trials as medical institutions prioritize the treatment of those afflicted with COVID-19. As we balance the commitment to treat our cancer patients while mitigating the risk of viral spread to patients, employees and their families, we have instituted protective policies consistent with guidelines provided by the Centers for Disease Control and Prevention at all TCR2 facilities. While we are committed to providing an interim update of the Phase 1 portion of the TC-210 Phase 1/2 clinical trial in the second quarter of 2020 and the Phase 1 portion of the TC-110 Phase 1/2 clinical trial in the second half of 2020, the effect of the COVID-19 pandemic may impact the exact timing or content of these interim updates.

TC-110 Clinical Trial Design

The Phase 1/2 clinical trial is evaluating the safety and efficacy of TC-110, TCR2’s TRuC-T cell targeting CD19. The trial is enrolling patients with CD19-positive B-cell hematological malignancies including aALL, DLBCL, FL and other NHL subtypes.

In the Phase 1 portion of the clinical trial, patients will receive increasing TC-110 T cell doses following lymphodepleting chemotherapy. The primary objective of the Phase 1 portion of the study is to assess safety with a key secondary objective to determine the recommended Phase 2 dose (RP2D).

In the Phase 2 portion of the clinical trial, approximately 60 patients are planned to receive TC-110 at the RP2D and will be stratified according to their cancer diagnosis in three distinct cohorts: aggressive NHL, indolent NHL and aALL. Approximately 20 patients per indication will be infused with TC-110 T cells.

In addition to standard assessments of safety and efficacy, a panel of translational assays will be performed on patient samples throughout both phases of the study to assess, among others, cytokine production as well as expansion, trafficking, persistence, and changes in immunophenotype of TC-110 T cells.

TC-110 Patient Opportunity

Adult ALL

In 2019, there were an estimated 5,900 cases of ALL and over 1,500 related deaths in the United States. Adults comprise approximately 45% of all ALL cases but make up more than 85% of ALL-related deaths. CD19 directed CAR-Ts are not approved for patients with aALL.

DLBCL

In 2019 there were an estimated 74,000 new cases of NHL and 20,000 related deaths in the United States. Approximately two-thirds of patients with DLBCL are cured of their disease with frontline chemoimmunotherapy (R-CHOP). However, refractory patients have a median overall survival of only 6.3 months.

CD19-directed CAR-T cell therapy has shown activity in heavily pre-treated patients with CD19-positive DLBCL and two CAR-T cell therapies, Kymriah and Yescarta, have been approved for that indication. However, the response rate six months post-infusion ranges from 37% to 41% and both therapies are associated with high rates of severe CRS (13% to 23%) and neurotoxicity (12% to 28%).

Follicular Lymphoma

Approximately 15,000 patients were diagnosed in the United States with FL in 2019. The clinical course of patients with FL is generally indolent. However, 20% of patients with FL relapse within two years of R-CHOP therapy and have a median five-year survival rate of only 50% compared to 90% for the remaining 80% of

patients with a longer response duration. The experience with CAR-T cell therapy in FL is much more limited than in ALL or DLBCL.

Anticipated Milestones

TCR2 anticipates an interim update from the Phase 1 portion of the TC-210 Phase 1/2 clinical trial for patients with mesothelin-expressing solid tumors in 2Q20.

TCR2 anticipates an interim update from the Phase 1 portion of the TC-110 Phase 1/2 clinical trial for patients with CD19+ non-Hodgkin lymphoma or adult acute lymphoblastic leukemia in 2H20.

TCR2 anticipates clinical production of TRuC-T cells at its manufacturing facility in Stevenage, UK, in 2H20.

TCR2 anticipates advancing a third mono TRuC-T cell therapy in 2Q20 with a target IND filing in 1H21.

Financial Highlights

Cash Position: TCR2 ended 2019 with $158.1 million in cash, cash equivalents, and investments compared to $123.2 million as of December 31, 2018. Net cash used in operations was $41.4 million for 2019 compared to $18.7 million for 2018. TCR2 projects net cash use of $60-70 million for 2020.

R&D Expenses: Research and development expenses were $37.5 million for 2019 compared to $19.7 million for 2018. The increase in R&D expenses is primarily related to increase in headcount, activities related to the Phase 1/2 clinical trial of the Company’s lead solid tumor product candidate, TC-210, and activities related to the IND submission of the Company’s lead hematologic cancer product candidate, TC-110.

G&A Expenses: General and administrative expenses were $13.9 million for 2019 compared to $6.8 million for 2018. The increase in general and administrative expenses was primarily due to an increase in personnel costs and costs associated with operations as a public company.

Net loss: Net loss was $47.6 million for 2019 compared to $24.3 million for 2018, driven predominantly by increased R&D expense for 2019.

Upcoming Events

TCR2 Therapeutics management are scheduled to participate at the following upcoming conferences.

Goldman Sachs Cell Therapy Day: Alfonso Quintás Cardama, M.D., Chief Medical Officer of TCR2 Therapeutics, will present using a virtual platform on Monday, April 6, 2020 at 2:00pm ET

On March 30, 2020 Euronext Growth: ALIMM), the specialist drug discovery and development company, is reported that subscriptions to raise £1.5 million (the "Subscriptions") through the issue of 15,000,000 new ordinary share of 10 pence each in the Company ("Ordinary Shares") (the "Subscription Shares") at a price of 10p per Ordinary Share ("Issue Price") (Press release, ImmuPharma, MAR 30, 2020, View Source [SID1234555982]). The Subscriptions comprise a £200,000 subscription from Dr Robert Zimmer, (Director, President & Chief Scientific Officer of ImmuPharma) through Luca and Associates AG ("Luca")( a company to which he is connected) and a £1.3 million subscription with Lanstead Capital Investors L.P. ("Lanstead"), an institutional investor and substantial shareholder, together with a related sharing agreement, to raise in aggregate £1.5 million before expenses.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Highlights

Subscription for 2,000,000 new Ordinary Shares (the "Luca Subscription") by Luca and Associates AG at an issue price of 10 pence per Subscription Share to raise gross proceeds of £200,000 (the "Luca Subscription").
Subscription for 13,000,000 new Ordinary Shares (the "Lanstead Subscription Shares") by Lanstead at an issue price of 10 pence per Subscription Share to raise gross proceeds of £1.3 million (the "Lanstead Subscription").
Further supportive investment in the Company by Lanstead following the £4.43 million investment and sharing agreement in February 2016, from which ImmuPharma ultimately received just over £5.0 million from Lanstead, and the £2.66 million investment in June 2019 which was invested in an ongoing sharing agreement with Lanstead, which is also currently ahead on cumulative settlements to date.
The Issue Price represents a 6.45 per cent. discount to the closing price (of 10.69p) of the Ordinary Shares on 27 March 2020, the latest business date prior to the Subscription.
The £1.3 million gross proceeds of the Lanstead Subscription will be pledged by the Company pursuant to a sharing agreement with Lanstead (the "Sharing Agreement"). The Sharing Agreement, details of which are set out below, entitle the Company to receive back those proceeds on a pro rata monthly basis over a period of 24 months, subject to adjustment upwards or downwards each month depending on the Company’s share price at the time. The Sharing Agreement provides the opportunity for the Company to benefit from positive future share price performance.
The Company has also agreed to issue to Lanstead 650,000 new Ordinary Shares (the "Value Payment Shares") in connection with the Sharing Agreement.
The proceeds of the Subscriptions receivable by the Company, of £1.5 million, of which £1.3m is subject to the Sharing Agreement, will be used primarily to fund:
– Expansion of the Company’s R&D programmes (see below); and
– General working capital.
Update on R&D Programmes

ImmuPharma’s pipeline will now comprise four therapy areas, which are Autoimmunity; Anti-Infectives; Metabolism and Cancer.

Highlights:

Strengthened advisory team for Lupuzor international Phase III trial;
Proof of Concept study planned for Lupuzor in CIDP patients;
3 new Anti-Infective programmes; and
New BioGlucagon product, with a potential market launch date in 2022.
Autoimmunity | Lupuzor for Lupus and CIDP

Lupus

The Company continues positively with its collaboration with our exclusive US partner Avion Pharmaceuticals LLC ("Avion"), who is fully funding the new optimised international Phase III trial for Lupuzor in lupus.

Recently, Avion has strengthened its team of advisors for the Phase III trial, entering into a collaboration with a leading lupus patient group and the formation of a Board of Key Opinion Leaders ("KOLs"), all of whom are senior respected consultants within the lupus and autoimmune community in the US and Europe.

In consultation with these advisors, a number of key decisions will now be made and next steps agreed in advance to meeting with the Food & Drug Administration (FDA). These will include:

Agreeing the structure of the optimised international Phase III Lupuzor trial;
Agreeing on the demographics and patient inclusion criteria; and
Guidance on key territories where the trial will be conducted
Once the Phase III trial has commenced, these advisors will together provide:

The support and expedition to identify and recruit the most appropriate lupus patients for the trial and;
Promotion to patient steering groups to raise awareness of Lupuzor to lupus patients and their clinicians throughout the duration of the trial.
Discussions continue with potential partners for Lupuzor outside of the US.

Chronic Inflammatory Demyelinating Polyneuropathy ("CIDP")

Outside of lupus the unique mechanism of action of Lupuzor (also known as Forigerimod or P140) has demonstrated in a number of pre-clinical trials that it has the potential to also be effective within other auto-immune diseases. One disease of key interest to ImmuPharma’s team is Chronic Inflammatory Demyelinating Polyneuropathy ("CIDP") where compelling pre-clinical data* has been generated. CIDP could potentially be granted ‘Orphan Drug Designation’ due to the unmet clinical need and with around 50,000 to 100,000 confirmed cases in the US and Europe, which would provide a fast approval process. The sales potential however could be greater than $500 million annually, with currently no effective approved drug on the market.

ImmuPharma is planning to commence a Proof of Concept study in CIDP patients based on the strong data already gained within the Company’s lupus dossier.

*Results were published in 2018 in the ‘Journal of Autoimmunity’ entitled: "An autophagy-targeting peptide to treat chronic inflammatory demyelinating polyneuropathies". This paper is available to review on line at the Journal of Autoimmunity: click here

Anti-Infectives

Why Anti-Infectives?

There is growing resistance to antibiotics and antifungal agents, and more recently the Covid-19 outbreak has highlighted mankind’s unpreparedness and susceptibility to more aggressive infectious microorganisms, not only from a health perspective but also from an economic and social impact. Surviving cancer and other fatal diseases is undoubtedly vital but without sufficient ammunition against bugs (viral, fungal or bacterial, ) we survive to face a bigger problem.

The World Health Organisation has stated that resistance to antibiotics is one of the biggest threats to global health, costs and mortality. Pandemic disease events could cost the global economy over $6 trillion in the 21st century (National Academy of Medicine: 2016).

However, despite the obvious threats to the health and wellbeing of the world’s population, anti-infectives is a therapy area that attracts one of the lowest R&D spends in the biopharma industry. For example, there are three trials in oncology for one in anti-infectives, even though anti-infective drug development is faster and less expensive. Trials are generally much shorter for anti-infection versus chronic disease. So, this is an attractive therapy area for speed to market and lower cost of trials.

Antiviral opportunity

The Company through its subsidiary UREkA Pharma has recently become a partner in a consortium dedicated to the development of novel peptides intended to block the fusion of COVID-19 and other viruses to the target cell, an approach similar to Fuzeon (enfuvirtide) by Roche.

Drugs that target viral entry into the host cell have been proven effective against a wide range of viral diseases. The aim is to apply the results of fundamental research to the development of novel inhibitors of SARS-CoV-2 entry into target cells using the Urelix patented technology of UREkA Pharma together with contributions from the other members of the consortium. The strategy is based on inhibiting viral entry, using peptides specific for the viral fusion protein.

Anti-fungal opportunity | ‘BioAMP-B’

ImmuPharma has recently developed BioAMP-B, a novel peptide-based drug that offers a potential improvement on Amphotericin-B ("Amp-B"). Amp-B is one of the few effective treatments for many serious and life threatening fungal infections such as aspergillosis (lung infection). However, the leading AMP-B, ‘Ambisome’ is known to cause serious kidney toxicity in 14-15% of patients. ImmuPharma’s BioAMP-B’s target profile has a superior safety profile to Ambisome. Sales of Ambisome in 2019 were $407 million. Next step is lead candidate optimisation.

Anti-bacterial opportunity | ‘IPP-203101’

IPP-203101 is ImmuPharma’s novel peptide-based antibiotic for the treatment of MRSA ("methicillin-resistant Staphylococcus aureus" or "superbug") and other severe and hospital acquired multi-resistant infections. MRSA infections are increasingly resistant to even the last lines of drug defence such as ‘vancomycin’ and ‘teicoplanin’, which are two commonly used antibiotics. IPP-203101 causes bacterial cell death by a two-step mechanism involving interaction with the lipid component of the membrane followed by membrane breakdown. IPP-203101’s target profile is to be as efficacious as vancomycin, but with a better safety profile, weekly administration, less susceptible resistance and a better efficacy profile for certain strains. Next step is lead candidate optimisation.

Metabolism | BioGlucagon

ImmuPharma has developed its product, BioGlucagon, as a potential new rescue therapy for low sugar events in diabetes. Existing glucagon products have poor solubility and are inconvenient with variable dosing due to poor solubility creating risks for patients. BioGlucagon has 100% solubility, can be formulated in pre-filled syringe pens and could be used in insulin pumps. The next step will be to progress towards a bio equivalence study for BioGlucgagon, which if successful could result with a potential market launch date in 2022.