On March 22, 2022 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported the discontinuation of ORIC-101 and also reported financial results and operational updates for the quarter and year ended December 31, 2021 (Press release, ORIC Pharmaceuticals, MAR 22, 2022, View Source [SID1234610602]). The company conducted planned interim analyses of two Phase 1b studies and concluded that ORIC-101 did not demonstrate sufficient clinical activity to warrant further development.

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"We are disappointed in the outcome of the ORIC-101 studies in combination with nab-paclitaxel in various solid tumors and in combination with enzalutamide in metastatic prostate cancer, two late-line patient populations for whom limited treatment options exist today. We believe both studies were well designed, allowing us to thoroughly and efficiently answer an important clinical question. With this decision to discontinue ORIC-101 development, we would like to thank the investigators, site staff, the ORIC team, and most importantly, patients and families who participated in the trials," said Pratik S. Multani, MD, chief medical officer.

"We’ve always been committed to rapid, data driven decision making and allocating resources efficiently and prudently," said Jacob M. Chacko, MD, chief executive officer, "We intentionally built a diverse pipeline of differentiated programs, which includes our Phase 1b single agent trials for ORIC-533, our orally bioavailable CD73 inhibitor, ORIC-114, our brain penetrant EGFR/HER2 inhibitor, and ORIC-944, our embryonic ectoderm development (EED) inhibitor. We expect to report initial data from each study in the first half of 2023. As a result of the ORIC-101 discontinuation, we project our cash runway to extend into the second half of 2024, well beyond the planned initial data disclosures from these three clinical programs."

Fourth Quarter 2021 and Other Recent Highlights

ORIC-101: Glucocorticoid Receptor Antagonist

Based on interim analyses from the two Phase 1b studies, ORIC-101 did not demonstrate sufficient clinical activity and, therefore, the company has discontinued further development.

The dose expansion portion of the Phase 1b clinical trial of ORIC-101 in combination with enzalutamide enrolled 28 patients at the recommended phase 2 dose (RP2D) with metastatic prostate cancer progressing on enzalutamide. The RP2D was well tolerated with a safety profile consistent with previously reported results. ORIC-101 in combination with enzalutamide did not translate into a meaningful clinical benefit, with a median progression-free survival (PFS) in the target patient population of 3.7 months.

The dose expansion portion of the Phase 1b clinical trial of ORIC-101 in combination with nab-paclitaxel enrolled 61 patients at the RP2D across four cohorts: pancreatic ductal adenocarcinoma (PDAC), ovarian cancer, triple negative breast cancer (TNBC), and other advanced solid tumors. The RP2D was well tolerated with a safety profile consistent with previously reported results. There were no objective responses in the PDAC cohort (n=21) and there was one confirmed partial response in the ovarian cancer cohort (n=13). There was no meaningful clinical benefit based on median PFS across all cohorts (PDAC: 1.9 months, and ovarian cancer: 2.2 months).

ORIC-533: CD73 Inhibitor
ORIC-533 is a highly potent, orally bioavailable small molecule inhibitor of CD73 and has demonstrated more potent adenosine inhibition in preclinical studies compared to an antibody approach and other small molecule inhibitors of the adenosine pathway.

Ex vivo human data supporting the therapeutic potential of single agent ORIC-533 in multiple myeloma were presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting.
Single agent activity in an autologous bone marrow mononuclear assay system from multiple myeloma patients showed CD73 inhibition compared favorably to approved therapies for the treatment of multiple myeloma, including lenalidomide, bortezomib and daratumumab.
A Phase 1b trial with ORIC-533 as a single agent in multiple myeloma is enrolling patients and initial data are expected to be reported in the first half of 2023.

ORIC-114: EGFR/HER2 Inhibitor
ORIC-114 is a brain penetrant, orally bioavailable, irreversible inhibitor designed to selectively target EGFR and HER2 with high potency against exon 20 insertion mutations.

Compelling brain exposure and antitumor activity of ORIC-114 in preclinical studies of HER2-positive breast cancer were presented at AACR (Free AACR Whitepaper)-NCI-EORTC.
Head-to-head data in an EGFR exon 20 NSCLC xenograft model were disclosed demonstrating good tolerability and improved efficacy, including a 90% complete response rate, with ORIC-114 versus multiple clinical stage exon 20 inhibitors.
The Clinical Trial Application (CTA) for ORIC-114 was filed in the fourth quarter of 2021 and was cleared by the regulatory authorities of the Republic of Korea in the first quarter of 2022.
A Phase 1b trial with ORIC-114 as a single agent has been initiated and will enroll patients with advanced solid tumors with EGFR or HER2 exon 20 alterations or HER2 amplification and will allow patients with CNS metastases that are either treated or untreated but asymptomatic. The company expects to report initial Phase 1b data from this trial in the first half of 2023.
ORIC-944: PRC2 Inhibitor
ORIC-944 is a potent and selective allosteric inhibitor of polycomb repressive complex 2 (PRC2) that targets its regulatory embryonic ectoderm development (EED) subunit and has demonstrated single agent efficacy in multiple enzalutamide-resistant prostate cancer models in preclinical studies.

The IND for ORIC-944 was cleared by the FDA in the fourth quarter of 2021.
A Phase 1b trial with ORIC-944 as a single agent will enroll patients with metastatic prostate cancer. The company expects to report initial Phase 1b data from this trial in the first half of 2023.
PLK4 Inhibitor Program
In March, the company announced a small molecule therapeutic program intended to address a mechanism of innate resistance found in a subset of breast cancers, specifically a synthetic lethal interaction of polo-like kinase 4 (PLK4) inhibition in tumors bearing a TRIM37 DNA amplification. Breast cancer models as well as other tumor models with this TRIM37 amplification have a key tumor dependency on PLK4 and our therapeutic approach is to selectively inhibit this enzyme.

Corporate
In November 2021, the company appointed Angie You, PhD, to its board of directors. Dr. You was most recently CEO of Amunix Pharmaceuticals, which was acquired by Sanofi, and brings broad experience spanning venture capital, business development and public company leadership roles.

Anticipated Program Milestones

ORIC anticipates the following upcoming milestones:

ORIC-533: Initial Phase 1b data in 1H 2023
ORIC-114: Initial Phase 1b data in 1H 2023
ORIC-944: Initial Phase 1b data in 1H 2023
Fourth Quarter and Full year 2021 Financial Results

Cash, Cash Equivalents and Investments: Cash, cash equivalents and investments totaled $280.4 million as of December 31, 2021, and with the discontinuation of ORIC-101, the company expects its cash runway to be extended into the second half of 2024.

R&D Expenses: Research and development (R&D) expenses were $16.7 million for the three months ended December 31, 2021, compared to $12.1 million for the three months ended December 31, 2020, an increase of $4.6 million. For the year ended December 31, 2021, R&D expenses were $56.9 million compared to $35.9 million for the same period of 2020, an increase of $20.9 million. The increases for the 2021 periods were primarily driven by an increase in external expenses related to the advancement of ORIC-101, ORIC-533 and our other product candidates, as well as higher personnel costs, including additional non-cash stock-based compensation of $0.7 million and $2.9 million for the three and twelve months ended December 31, 2021, as compared to the same periods in 2020, respectively.

G&A Expenses: General and administrative (G&A) expenses were $6.1 million for the three months ended December 31, 2021, compared to $4.3 million for the three months ended December 31, 2020, an increase of $1.8 million. For the year ended December 31, 2021, G&A expenses were $22.0 million compared to $13.4 million for the same period in 2020, an increase of $8.6 million. These increases were primarily due to higher personnel costs, including additional non-cash stock-based compensation of $1.1 million and $4.6 million for the three and twelve months ended December 31, 2021, as compared to the same periods in 2020, respectively, and higher costs related to operating as a public company.
Webcast and Conference Call

ORIC will host a conference call and webcast today at 5:00 p.m. ET. To participate in the conference call, please dial (833) 651-0991 (domestic) or (918) 922-6080 (international) and refer to conference ID 8637367. A live webcast and audio archive of the conference call will be available through the investor section of the company’s website at www.oricpharma.com. The webcast will be available for replay for 90 days following the presentation.

On March 22, 2022 Telix Pharmaceuticals Limited (ASX: TLX, Telix, the Company) reported it has made significant progress in advancing the Company’s glioblastoma multiforme (GBM) therapy candidate TLX101 into the next stage of clinical development (Press release, Telix Pharmaceuticals, MAR 22, 2022, View Source [SID1234610619]).

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TLX101 (4-L-[131I] iodo-phenylalanine, or 131I-IPA) is one of the Company’s lead therapeutic clinical programs and has been granted orphan drug designation in the US and Europe. TLX101 targets L-type amino acid transporter 1 (LAT-1), typically over-expressed in GBM.

The IPAX-1 Phase I study, which completed recruitment in 2021,[1] established a favourable safety profile for TLX101 and promising preliminary disease stabilisation with evidence of anti-tumour responses in a second-line (refractory) disease setting.[2]

Building on this experience, Telix has now been granted Human Research Ethics Committee (HREC) approval to commence a Phase I dose escalation study (called "IPAX-2") to evaluate TLX101 in combination with post-surgical standard of care comprised of external beam radiation therapy (EBRT) and temozolomide in newly diagnosed GBM patients. Twelve patients are expected to be recruited to evaluate whether the observed safety and drug interaction profile remains suitable in this setting before progressing to a Phase II study.

Professors Hui Gan and Andrew Scott, of the Olivia Newton-John Cancer Research Institute at Melbourne’s Austin Health, are the Principal Investigators for IPAX-2. TLX101-CDx (18F-FET PET[3]) will be used for imaging in the study to identify participants with over-expressed LAT-1 as suitable candidates for 131I-IPA therapy, and to provide baseline and follow up information on tumour response and progression.

In addition to the Company-sponsored IPAX-2 study, Kepler University Hospital in Linz (Austria) has received ethics approval to commence an institution-led Phase II study of TLX101 (called "IPAX-Linz", or "IPAX-L") in combination with EBRT in patients with relapsed-glioblastoma. This provides an opportunity to continue to study the benefit to patients in the recurrent (second line) setting, building on the experience of the IPAX-1 study at this leading neuro-oncology site in Europe.

The IPAX-L study will commence enrolling patients as early as March 2022. IPAX-L is being led by Dr Josef Pichler and will supplement the experience obtained from Telix’s IPAX-1 study in which Dr Pichler was also a Principal Investigator. Telix is supporting IPAX-L through the contribution of investigational product and funding.

Dr Colin Hayward, Chief Medical Officer of Telix Pharmaceuticals stated, "Running these concurrent studies will build on the promising data generated in the IPAX-1 study, supporting our goal to expedite the development of a potential new therapy in an aggressive cancer with limited therapeutic options. With IPAX-2 Telix is taking the development of TLX101 into the front-line setting for the first time. Following the promising insights from the previous IPAX-1 study we are excited to see the potential impact of targeted radiation in patients after their initial surgery.

"We are also very pleased to support Dr Pichler and his team at Kepler University Hospital, to continue the important clinical research into TLX101 in the second-line setting and build on the IPAX-1 experience to explore new therapeutic options for glioblastoma patients."

Dr Josef Pichler, Kepler University Hospital, Austria, Principal Investigator in the IPAX-L study added, "Based on extensive experience with this asset in the IPAX-1 study, I am convinced that TLX101 should be further investigated for the treatment of brain tumours. The first clinical data has shown encouraging results with a good safety profile. IPAX-Linz will gather additional data on safety and preliminary activity results."

On March 22, 2022 MorphoSys AG (FSE: MOR; NASDAQ: MOR) and Incyte (Nasdaq: INCY) reported that the Swiss agency for therapeutic products (Swissmedic), has granted temporary approval for Minjuvi(R) (tafasitamab) in combination with lenalidomide, followed by Minjuvi monotherapy, for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), after at least one prior line of systemic therapy including an anti-CD20 antibody, who are not eligible for autologous stem cell transplant (ASCT) (Press release, MorphoSys, MAR 22, 2022, View Source [SID1234610750]). Incyte holds exclusive commercialization rights for Minjuvi in Switzerland.

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"The approval of Minjuvi by Swissmedic is excellent news," said Jonathan Dickinson, Executive Vice President and General Manager, Incyte Europe. "There are a substantial number of people living with relapsed or refractory DLBCL in Switzerland and we’re pleased to be able to offer them a new treatment option."

"DLBCL is a fast-growing cancer and can be very hard to treat. Up to 40% of DLBCL patients either relapse after they have been treated or don’t respond to initial treatment at all," said Mike Akimov, M.D., Ph.D., Head of Global Drug Development, MorphoSys. "Minjuvi addresses this unmet need and its approval in Switzerland is a crucial milestone for these patients."

The approval is based on the results from the L-MIND study evaluating the safety and efficacy of tafasitamab in combination with lenalidomide as a treatment for patients with relapsed or refractory DLBCL who are not eligible for autologous stem cell transplant (ASCT). The results showed a best objective response rate (ORR) of 56.8% (primary endpoint), including a complete response (CR) rate of 39.5% and a partial response rate (PR) of 17.3%, as assessed by an independent review committee. The median duration of response (mDOR) was 43.9 months after a minimum follow up of 35 months (secondary endpoint). Tafasitamab together with lenalidomide was shown to provide a clinically meaningful response and the side effects were manageable.[2]

Incyte and MorphoSys share global development rights to tafasitamab; Incyte has exclusive commercialization rights to tafasitamab outside the U.S. Tafasitamab is co-marketed by Incyte and MorphoSys under the brand name Monjuvi(R) (tafasitamab-cxix) in the U.S., and is marketed by Incyte under the brand name Minjuvi in Europe, the UK and Canada.

About Diffuse Large B-Cell Lymphoma
DLBCL is the most common type of non-Hodgkin lymphoma in adults worldwide, comprising 40% of all cases[3]. Each year around 16,000 patients in Europe are diagnosed with relapsed or refractory DLBCL[4],[5],[6]. The condition is characterized by rapidly growing masses of malignant B-cells in the lymph nodes, spleen, liver, bone marrow or other organs[7]. It is an aggressive disease with about one in three patients not responding to initial therapy or relapsing thereafter[8],[9],[10],[11].

About L-MIND
The L-MIND trial is a single arm, open-label Phase 2 study (NCT02399085) investigating the combination of tafasitamab and lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have had at least one, but no more than three prior lines of therapy, including an anti-CD20 targeting therapy (e.g., rituximab), who are not eligible for high-dose chemotherapy (HDC) or autologous stem cell transplant (ASCT). The study’s primary endpoint is overall response rate (ORR). Secondary outcome measures include duration of response (DoR), progression-free survival (PFS) and overall survival (OS). The study reached its primary completion in May 2019.

For more information about L-MIND, visit View Source

About Minjuvi(R) (tafasitamab)
Tafasitamab is a humanized Fc-modified CD19 targeting monoclonal antibody. In 2010, MorphoSys licensed exclusive worldwide rights to develop and commercialize tafasitamab from Xencor, Inc. Tafasitamab incorporates an XmAb(R) engineered Fc domain, which mediates B-cell lysis through apoptosis and immune effector mechanism including Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) and Antibody-Dependent Cellular Phagocytosis (ADCP).

In the U.S., Monjuvi(R) (tafasitamab-cxix) is approved by the U.S. Food and Drug Administration in combination with lenalidomide for the treatment of adult patients with relapsed or refractory DLBCL not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant (ASCT). This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

In Europe, Minjuvi(R) (tafasitamab) received conditional approval, in combination with lenalidomide, followed by Minjuvi monotherapy, for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for autologous stem cell transplant (ASCT).

Tafasitamab is being clinically investigated as a therapeutic option in B-cell malignancies in several ongoing combination trials.

Minjuvi(R) and Monjuvi(R) are registered trademarks of MorphoSys AG. Tafasitamab is co-marketed by Incyte and MorphoSys under the brand name Monjuvi(R) in the U.S., and marketed by Incyte under the brand name Minjuvi(R) in Europe, the UK and Canada.

XmAb(R) is a registered trademark of Xencor, Inc.

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).

On March 22, 2022 Evaxion Biotech A/S (NASDAQ: EVAX) ("Evaxion" or the "Company"), a clinical-stage biotechnology company specializing in the development of AI-driven immunotherapies, repoted the fourth quarter and full-year 2021 financial results and provided an operational update (Press release, Evaxion Biotech, MAR 22, 2022, View Source [SID1234610580]).

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Lars Wegner, CEO of Evaxion, said: "Evaxion continued to demonstrate exciting clinical momentum in the fourth quarter of 2021, beginning a clinical collaboration with Merck for a new Phase 2b trial, combining EVX-01 and Merck’s KEYTRUDA, to address a significant unmet medical need. On January 18, 2022, we received Australian clearance to begin this Phase 2b trial, which is a significant step forward for Evaxion and our exciting pipeline of immunotherapies. Data from the previous Phase 1/2a trial have shown that EVX-01 may be able to improve the treatment landscape in melanoma and possibly other cancers and we are excited to continue the clinical progress of our lead product candidate EVX-01 in collaboration with Merck. Our cash reserves of $32.2 million as of the end of the fourth quarter provide a solid financial foundation and will facilitate the continued development of our lead programs."

Operational and Business Highlights in the Fourth Quarter of 2021

Completed FPO of 3,942,856 ordinary shares represented by ADSs raising net proceeds of $24.9 million after deducting underwriting discounts, commissions and other offering expenses
Announced clinical trial collaboration and supply agreement with Merck to evaluate the combination of Evaxion’s cancer immunotherapy EVX-01 with KEYTRUDA in Phase 2b clinical trial in patients with metastatic melanoma
Awarded this year’s Enabling Technology Leadership Award in the artificial intelligence-enabled drug discovery industry by global research and consulting firm Frost & Sullivan
Presented at the Immuno UK 2021 conference held in London in October
Events after the Reporting Period

Received regulatory clearance to initiate phase 2b trial of EVX-01 in combination with KEYTRUDA for treatment of metastatic melanoma
Completed recruitment for Phase 1/2a clinical trial for EVX-02, advancing into a dedicated Phase 2b clinical adjuvant trial in patients with resectable melanoma
Announced publication on personalized therapy with EVX-01 in patients with metastatic melanoma in open access, peer-reviewed journal OncoImmunology
Announced leadership changes for Chief Operating Officer and Chief Financial Officer
Received first tranche €7.0 million (approximately $7.7 million) from our European Investment Bank (EIB) loan in February 2022
Expected milestones in 2022

Phase 2b first patient, first visit with EVX-01 for metastatic melanoma (peptide-based, personalized cancer therapy)
Phase 2b regulatory filing for EVX-02/03 in patients with resectable melanoma (DNA-based, personalized cancer therapy)
Phase 2b first patient, first visit with EVX-02/03
Phase 1 regulatory filing for EVX-B1 (S. aureus) in skin and soft tissue infections
Second bacteria target selected from EDEN platform
First viral candidate selected from RAVEN platform
Full Year 2021 Financial Results

Cash position: As of December 31, 2021, cash and cash equivalents were $32.2 million as compared to $5.8 million as of December 31, 2020. On November 9, 2021, we closed our FPO raising net proceeds of $24.9 million after deducting underwriting discounts, commissions and other offering expenses.
Research and Development expenses were $19.6 million for the year ended December 31, 2021 as compared to $10.9 million for the year ended December 31, 2020. The increase was primarily related to increased spending, net of grant income, for ongoing development on our platform, preclinical product candidates, and clinical trials. In addition, employee-related costs increased due to higher headcount.
General and Administrative expenses were $6.3 million for the year ended December 31, 2021 as compared to $5.7 million for the year ended December 31, 2020. The increase was primarily due to an increase in professional fees related to the expansion of our corporate function for our Initial Public Offering (IPO), partially offset by a decrease in employee-related costs.
Net loss was $24.5 million for the year ended December 31, 2021 or ($1.26) loss per basic and diluted share as compared to $15.0 million, or ($0.97) loss per basic and diluted share for the year ended December 31, 2020.
Guidance

We expect the net proceeds from our IPO, our FPO, funds from draws on amounts available under our EIB loan and our existing cash and cash equivalents will be sufficient to fund our operating expenses and capital expenditure requirements through at least 12 months subsequent to the date of our 2021 annual report.
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KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. Kenilworth, NJ, USA.