On March 22, 2022 Mission Therapeutics ("Mission"), a drug discovery and development company focused on protein homeostasis by selectively inhibiting deubiquitylating enzymes (DUBs), reported that Dr Paul Wallace, Chief Business Officer, will attend the sixteenth annual BIO-Europe Spring conference (28-31 March) (Press release, Mission Therapeutics, MAR 22, 2022, View Source [SID1234610561]).

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BIO-Europe Spring is one of the most international gatherings in the biopharma industry, bringing together the life science community for global dealmaking. Dr Paul Wallace will join participants from other leading companies in the sector, attending meetings, panel discussions, and showcases, and is available for one-to-one meetings. The event is being held virtually.

On March 22, 2022 MannKind Corporation (Nasdaq: MNKD), a company focused on the development and commercialization of inhaled therapeutic products for patients with endocrine and orphan lung diseases, reported that its Chief Scientific Officer, Thomas Hofmann, MD, PhD, will participate in the Cantor Virtual Rare Orphan Disease Summit on Tuesday, March 29, 2022 at 8:00 am (PT) (Press release, Mannkind, MAR 22, 2022, View Source [SID1234610560]).

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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

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If you have interest in participating in the Cantor Virtual Rare Orphan Disease Summit, please reach out to your Cantor Fitzgerald representative.

On March 22, 2022 Lantern Pharma Inc. (NASDAQ: LTRN), a clinical stage biopharmaceutical company using its proprietary RADR artificial intelligence ("A.I.") and machine learning (ML) platform to transform the cost, pace, and timeline of oncology drug discovery and development, reported that its Board of Directors has authorized an extension through July 31, 2022 of Lantern’s existing share repurchase program to acquire up to $7 million of the Company’s common stock (Press release, Lantern Pharma, MAR 22, 2022, View Source [SID1234610559]).

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Since the initiation of the share repurchase program in November 2021, a total of 475,157 shares of common stock have been repurchased pursuant to Lantern’s share repurchase program. Total expenditures for share repurchases from the time of initiation of the share repurchase program through March 21, 2022 were approximately $3.4 million, including purchase fees. Lantern is authorized to purchase up to an additional $3.6 million of the Company’s common stock pursuant to the repurchase program. As of December 31, 2021, Lantern had cash, cash equivalents and marketable securities of approximately $70.7 million.

The Company may purchase common stock on the open market, through privately negotiated transactions, or otherwise, in compliance with the rules of the United States Securities and Exchange Commission and other applicable legal requirements. The timing, amount of shares repurchased and prices paid for the stock under the repurchase program will depend on market conditions as well as corporate and regulatory limitations, including blackout period restrictions. The repurchase program does not obligate the Company to acquire any particular amount of shares, and the repurchase program may be suspended or discontinued at any time at the Company’s discretion.

On March 22, 2022 Plus Therapeutics, Inc. (Nasdaq: PSTV) (the "Company"), a clinical-stage pharmaceutical company developing innovative, targeted radiotherapeutics for rare and difficult-to-treat cancers, reported that the first patient has been dosed in the ReSPECT-LM Phase 1/2a dose escalation clinical trial of Rhenium-186 NanoLiposome (186RNL) for the treatment of patients with leptomeningeal metastases (LM) (Press release, Cytori Therapeutics, MAR 22, 2022, View Source [SID1234610558]).

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The investigational drug, 186RNL, is a proprietary nanoscale compound with a unique chelated radioisotope that is administered locally as a single dose via a conventional Ommaya reservoir. Rhenium-186 is a dual energy emitter (beta and gamma) with a short average path length for high precision, low dose rate that is safer for normal tissues, and high radiation density that overwhelms innate DNA repair mechanisms. The dual energy emission allows real time evaluation and monitoring of the 186RNL administration.

The disease target, solid tumor-originating LM, is a deadly and increasingly common central nervous system (CNS) complication potentially from all solid cancer, with breast cancer, lung cancer, gastrointestinal cancer and melanoma being the most common primary sources of LM, with 110,000 cases diagnosed annually in the U.S. LM affects the membranes (meninges) surrounding the brain and spinal cord. There are currently no meaningfully effective Food and Drug Administration-approved treatments.

"The rationale for use of 186RNL in LM patients is scientifically quite attractive, and in clinical practice was very straightforward to administer to our first patient," said Michael Youssef, M.D., Assistant Professor of Neuro-Oncology at University of Texas Southwestern and site Principal Investigator. "Quality of life and survival rates are poor among patients diagnosed with LM from solid tumors. With no standard of care, this represents a true unmet medical need in neuro-oncology."

"LM affects about 10 times the number of patients as glioblastoma but carries a substantially worse prognosis," said Norman LaFrance, M.D., Chief Medical Officer and SVP of Plus Therapeutics. "Initiating treatment in LM patients with 186RNL marks an important milestone for Plus Therapeutics and potentially for the LM patient population."

The ReSPECT-LM trial (NCT05034497) is a multicenter, sequential cohort, open-label, single dose, dose escalation Phase 1/2a study using a modified Fibonacci 3+3 study design. It will evaluate the maximum tolerated dose (MTD), maximum feasible dose (MFD), safety and efficacy of a single administration of 186RNL via intraventricular catheter for LM following standard surgical, radiation and/or chemotherapy treatment. The primary endpoints of the study are the incidence and severity of adverse events/serious adverse events and dose limiting toxicities. Secondary endpoints include overall response rate, duration of response, progression free survival and overall survival.

The ReSPECT-LM Phase 1/2a clinical trial follows preclinical studies in which tolerance to doses of 186RNL as high as 1,075 Gy was shown in animal models with LM with no observed significant toxicity. Treatment led to marked reduction in tumor burden in two animal models of LM.

The Company recently announced the FDA granted Fast Track designation to 186RNL for the treatment of LM. Fast Track designation confers several benefits to the drug development program including 1) more frequent meetings with and written communication from FDA, 2) eligibility for Accelerated Approval and Priority Review, if relevant criteria are met, and 3) Rolling Review, which allows a drug company to submit completed sections of its New Drug Application (NDA) for review by FDA, rather than wait until every section of the NDA is completed before the entire application can be reviewed.

About Leptomeningeal Metastases (LM)

LM is a rare complication of cancer in which the disease spreads to the membranes (meninges) surrounding the brain and spinal cord. LM occurs in approximately 5% of people with cancer and is usually terminal with one-year and two-year survival of just 7% and 3% respectively. LM can originate from solid tumors, primary brain tumors, or hematological malignancies.

On March 22, 2022 AC Immune SA (NASDAQ: ACIU), a clinical-stage biopharmaceutical company pioneering precision medicine for neurodegenerative diseases, reported its financial results for the year ended December 31, 2021, and provided a corporate update, highlighting progress in its broad pipeline of products to treat and diagnose neurodegenerative diseases (Press release, AC Immune, MAR 22, 2022, View Source [SID1234610557]).

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Prof. Andrea Pfeifer, CEO of AC Immune SA, commented: "We are off to a strong start in 2022 with the second of seven clinical data readouts presented last week at the AD/PD 2022 conference. The first-in-human study of our alpha-synuclein diagnostic, ACI-12589, showed it has strong potential to become the first reliable and accurate PET tracer for alpha-synucleinopathies (e.g. multiple system atrophy, MSA)."

"Pairing cutting-edge diagnostics with highly targeted and selective therapeutic agents, such as our vaccines targeting alpha-synuclein, phosphorylated-Tau, and Abeta, which are all advancing into later-stage development this year, we aim to shift the therapeutic paradigm of neurodegenerative diseases towards earlier, more accurate diagnosis, treatment, and prevention," Prof. Pfeifer said.

2021 and Subsequent Highlights

Pipeline progress

Tau

▪Expanded the Phase 1b/2a trial evaluating the first-in-class anti-phosphorylated-Tau (pTau) vaccine candidate ACI-35.030 for the treatment of AD in collaboration with Janssen Pharmaceuticals, Inc. The decision to expand the trial, which was made to support plans to advance ACI-35.030 into late-stage development, was based on encouraging interim safety, tolerability, and immunogenicity results. These showed that ACI-35.030 treatment was well tolerated and led to the strong induction of antibodies specific for pathological forms of Tau such as pTau and its aggregated form, enriched paired helical filaments (ePHF).

▪Top line data from the Phase 2 Lauriet trial of semorinemab in mild-to-moderate AD presented at CTAD 2021 showed a statistically significant (p=0.0008) 42.2% reduction in cognitive decline vs. placebo as measured by ADAS-Cog11 at week 49, one of the trial’s co-primary endpoints. There were no statistically significant differences between semoribemab and placebo arms in the other co-primary endpoint, ADCS-ADL, or in the secondary endpoints (MMSE and CDR-SB). AC Immune’s partner Genentech, a member of the Roche Group, is continuing with the trial’s open-label extension. Additional fluid biomarker data are expected in H2 2022.

Abeta

▪Presented full results from the landmark Phase 1b clinical trial evaluating the anti-Abeta vaccine ACI-24 in subjects living with Down syndrome (DS) at the Alzheimer’s Association International Conference (AAIC) 2021. These results showed evidence of immunogenicity and pharmacodynamic response following ACI-24 treatment and demonstrated its favorable safety and tolerability profile.

▪Presented at CTAD 2021 full results of the Phase 2 study evaluating ACI-24 in patients with mild AD. This assessment confirmed earlier results showing no safety concerns nor evidence of inflammation or ARIA (amyloid-related imaging abnormalities) related to ACI-24 in any subject.

▪New data on the optimized formulation of ACI-24 were published in a peer reviewed journal Brain Communications. The optimized formulation was well tolerated in preclinical models and generated a broad polyclonal anti-Abeta response with high titers of antibodies against neurotoxic pyroglutamate Abeta (pyroGlu-Abeta), a major component of Abeta plaques. Additional preclinical data on optimized ACI-24 were presented at AD/PD 2022 confirming its enhanced and sustained immunogenicity against another key pathological Abeta species, oligomeric Abeta.

A-syn

▪Clinical PET image analyses and preclinical studies were presented at AD/PD 2022 suggest that ACI-12589 was retained in brain areas affected by disease processes involving a-synuclein (a-syn) aggregation, indicating the product-candidate has potential as the first non-invasive diagnostic for alpha-synucleinopathies (e.g. MSA).

▪Completed all-stock acquisition of Affiris’ portfolio of therapeutics targeting a-syn, notably PD01, a clinically validated active vaccine candidate that places AC Immune at the forefront of Parkinson’s disease (PD) drug development. ACI-7104, the optimized formulation of PD01, is on track to enter Phase 2 testing in early PD patients in H2 2022.

▪Identified and characterized the first biologically active small molecule Morphomer a-syn aggregation inhibitors, showing that they significantly decreased a-syn aggregate formation in cellular assays by interfering with the fibrillation process.

NLRP3

▪Reported key advancements for several therapeutic discovery programs targeting the (NOD)-like receptor protein 3 (NLRP3) inflammasome. Small molecule Morphomer inhibitors of NLRP3 showed the first evidence of in vivo activity in a model of peripheral inflammation, while high-affinity SupraAntigen monoclonal antibodies were shown to bind extracellular components (ASC) of the NLRP3 pathway and inhibit inflammasome-mediated immune responses in vitro.

Strenthening Financial Position and Extend Shareholder Base

▪Strengthened cash position via an equity financing, adding the three lead investors in Covid-19 vaccine innovator BioNTech SE, Athos Service GmbH (Strüngmann family office), First Capital Partner GmbH (Egger Family Office), and MIG Fonds, as part of the Affiris deal.

Strengthening of Board

▪Appointed Alan Colowick, M.D., Monica Shaw, M.D., and Prof. Monika Bütler, Dr. oec., to the Company’s Board of Directors. Dr. Colowick is a biotech and investment executive with more than 20 years of experience in large and emerging biotech companies. Dr. Shaw is a pharmaceutical industry expert who has been involved in advancing more than 15 therapeutic products from first-in-human studies through commercialization. Prof. Bütler is a leading Swiss economist and former Vice President of the independent Swiss COVID-19 Science Taskforce.

Thought Leadership and Collaborations

▪Swiss Economic Forum (SEF) awarded AC Immune Co-Founder and CEO Prof. Andrea Pfeifer with the first SEF.WomenAward for CEO of the Year. This award recognizes women with an excellent entrepreneurial track record, giving greater prominence to role models who can inspire the next generation of businesswomen.

▪Expanded the Company’s research collaboration with leading scientists at the Center for Neurodegenerative Disease Research at the Perelman School of Medicine at the University of Pennsylvania. This partnership aims to advance therapeutic strategies targeting TAR DNA-binding protein 43 (TDP-43), a major driver of neurodegenerative diseases.

▪Received two Michael J. Fox Foundation grants to accelerate the development of first-in-class brain penetrant small molecules to inhibit alpha-synuclein aggregation and NLRP3 inflammasome activation in PD.

Our strategy for 2022
AC Immune’s execution strategy is to advance late-stage AD programs with partners, accelerate its non-AD and NeuroOrphan programs in-house, and advance development of its suite of potentially best-in-class diagnostics to enable precision medicine. The Company intends to maintain program leadership over its wholly-owned AD and PD vaccine programs until Phase 3 or beyond, and expects to initiate two mid-stage clinical trials in 2022:

▪ACI-7104 anti-a-syn vaccine candidate is on track to enter an adaptive, placebo-controlled, and biomarker-based Phase 1b/2 study in patients with early PD in H2 2022. The two part study will evaluate safety, immunogenicity, and measure biomarkers of pathological alpha-synuclein in Part 1, with a seamless transition to Part 2, which will aim to establish clinical proof-of-concept by monitoring progression of PD symptoms and biomarkers.

▪Optimized ACI-24 Abeta vaccine is on track to enter a placebo-controlled Phase 1b/2 study evaluating different dosing regimens vs. placebo in up to four cohorts of patients with AD before being expanded to a separate cohort of people living with DS to address DS-related AD. Key outcome measures for the study will include assessments of safety, immunogenicity, pharmacodynamics, target engagement, Abeta-PET and clinical outcomes.

2022 Clinical Milestones

ACI-12589
a-syn-PET tracer

Reported results from first-in-human study at AD/PD 2022 conference

ACI-35.030
anti-pTau vaccine

Reported Phase 1b/2a interim analysis from highest dose group in Q1; disclose future late-stage development plans in H2

ACI-24 (optimized)
anti-Abeta vaccine

ACI-24 (optimized vaccine formulation) Phase 1b/2a First-Patient-In (AD) in H1
Phase 1b in AD readout and decision to move into DS in H2

Crenezumab
anti-Abeta antibody

Top line Phase 2 results from AD prevention trial in patients with autosomal dominant AD in H1

Semorinemab
anti-Tau antibody

Additional fluid biomarker data from the Phase 2 Lauriet study in mild-to-moderate AD in H2

PI-2620
Tau-PET tracer

Phase 2 and Phase 1 results in AD and progressive supranuclear palsy (PSP) respectively, in H2

ACI-7104
anti-a-syn vaccine

Initiate Phase 2 trial in early PD in H2

Analysis of Financial Statements for the year ended December 31, 2021

▪Cash Position: The Company had a total cash balance of CHF 198.2 million, composed of CHF 82.2 million in cash and cash equivalents and CHF 116.0 million in short-term financial assets. This compares to a total cash balance of CHF 225.9 million as of December 31, 2020. The Company’s cash balance provides enough capital resources to progress through at least Q1 2024 without consideration of potential incoming milestone payments.

▪Contract Revenues: The Company did not record contract revenues for the year ended December 31, 2021, a decrease of CHF 15.4 million from the comparable period in 2020. The overall decrease is predominantly related to a CHF 10 million milestone payment as well as CHF 4.3 million associated with R&D activities in our agreement with Lilly that were recognized in 2020 and did not repeat in the current period.

▪R&D Expenditures: R&D expenses increased by CHF 2.8 million for the year ended December 31, 2021, to CHF 62.3 million.

oDiscovery and preclinical expenses (- CHF 0.4 million): The Company decreased expenditures across a variety of its discovery and preclinical programs. This was predominantly led by a decrease in investment for the research of alpha-synuclein antibodies and other discovery programs.

oClinical expenses (- CHF 2.3 million): The Company decreased expenditures across multiple clinical programs, notably for Phase 1 activities associated with our Morphomer Tau compound and expenses. These decreases were offset predominantly by ACI-35.030, which was driven by R&D cost sharing and increased patient enrollments into the Phase 1b/2a study.

oSalary- and benefit-related costs (+ CHF 2.3 million): The Company’s salary- and benefit-related costs increased primarily due to the internal reallocation of certain employees’ salaries and the annualization of 2020 hires.

▪G&A Expenditures: For the year December 31, 2021, G&A decreased by CHF 0.6 million to CHF 17.9 million. This decrease is predominantly related to a reallocation of CHF 2.8 million of certain IT and facilities costs offset by transaction costs incurred to complete the asset acquisition for Affiris’ alpha-synuclein portfolio.

▪Other Operating Income: The Company recognized CHF 1.2 million in grant income for R&D activities performed under our Michael J. Fox Foundation for Parkinson’s Research (MJFF) and Target ALS grants, a decrease of CHF 0.1 million compared to the prior period.

▪IFRS Loss for the Period: The Company reported a net loss after taxes of CHF 73.0 million for the year ended December 31, 2021, compared with a net loss of CHF 61.9 million for the comparable period in 2020.

2022 Financial Guidance

▪For the full year 2022, the Company expects its total cash burn to be in the range, CHF 75 million to CHF 80 million. The Company defines cash burn as operating expenditures adjusted to include capital expenditures and offset by significant non-cash items (including share-based compensation and depreciation expense).