On August 26, 2021 Starpharma (ASX: SPL, OTCQX: SPHRY) reported its annual report and financial results for the year ended 30 June 2021 (Press release, Starpharma, AUG 26, 2021, View Source [SID1234586932]).

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Financial Results

Cash position at 30 June 2021 of $60.5M
Net cash burn[1] of $16.5M[2] (FY20: $2M)
Receipt of $5.7M R&D tax incentive
Total revenue and other income of $3.5M (FY20: $7.1M); Revenue in the prior year included $4.3 million from AstraZeneca for a US$3 million development milestone
Reported loss of $19.7M (FY20: $14.7M)
Key activities

VIRALEZE

Developed VIRALEZE, a novel antiviral nasal spray using already approved agent, SPL7013, and undertook scale-up, manufacturing, and other supply chain activities, ahead of launch.
Registered VIRALEZE in Europe and India, and progressed regulatory activities for countries in multiple other regions.
On 25 March 2021, signed a sales and distribution agreement for VIRALEZE with LloydsPharmacy, one of the largest pharmacy groups in the UK.
LloydsPharmacy launched VIRALEZE in the UK online on 30 March 2021 and in-store in April 2021.
Starpharma launched VIRALEZE in countries in Europe in May 2021 via its dedicated product webstore.
Advanced commercial discussions for local distribution arrangements for VIRALEZE in India and in a number of other countries, including various European countries and other international regions.
Conducted extensive antiviral testing on the VIRALEZE antiviral agent:
Confirmed SPL7013 is virucidal against important coronavirus SARS-CoV-2[3] variants Delta, Alpha, Gamma, Beta and Kappa, in laboratory studies.
Demonstrated potent activity of SPL7013 against respiratory pathogen RSV (respiratory syncytial virus) and influenza, in laboratory studies, further expanding the potential uses for VIRALEZE.
Confirmed SPL7013 is active against other pandemic respiratory viruses "SARS" and "MERS", in laboratory studies, supporting the potential use of VIRALEZE in future pandemics.
Published extensive antiviral data for SPL7013 (the antiviral agent in VIRALEZE) in the prestigious international scientific journal, Antiviral Research[4].
In a SARS-CoV-2 challenge in vivo in a humanised mouse model of coronavirus infection, VIRALEZE administered nasally reduced viral load by >99.9% (vs. saline control) in the lungs and trachea of animals challenged with SARS-CoV-2.
Awarded $1 million in matched funding by the Australian Government’s Medical Research Future Fund (MRFF) Biomedical Translation Bridge (BTB) Program to expedite development and commercialisation of VIRALEZE.
Successfully completed a clinical safety study in humans, in which VIRALEZE was safe and very well tolerated, with no absorption of SPL7013 into the bloodstream
DEP Drug Delivery Platform

AstraZeneca expedited and expanded its DEP AZD0466 clinical program, into a multi‑region phase 1/2 trial, with an initial focus on haematological cancers to support rapid development and registration.
Continued progress and recruitment into DEP irinotecan phase 2 trial, with 54 patients now recruited, with multiple patients exhibiting encouraging efficacy signals observed, including impressive tumour shrinkage and reductions in tumour marker levels for multiple tumour types, including breast, colorectal, ovarian, pancreatic, lung and oesophageal cancer. Clinical trial preparations continue for the addition of combinations with DEP irinotecan, thereby expanding the potential market opportunity.
Continued progress and recruitment into DEP docetaxel clinical trials with 50 patients now recruited and with multiple patients exhibiting encouraging efficacy signals observed, including prolonged stable disease, significant tumour shrinkage, reductions in tumour marker levels including in patients with hard-to-treat tumours such as pancreatic, oesophageal, cholangiocarcinoma, and gastric cancer.
Continued progress and recruitment into DEP cabazitaxel phase 2 trial with 42 patients now recruited and with multiple patients exhibiting efficacy signals in prostate cancer, including radiological responses, significant reductions in prostate-specific antigen (PSA) and lack of new bone metastases. Multiple heavily pre-treated patients also exhibited efficacy signals in gastro-oesophageal, ovarian, cholangiocarcinoma, lung, thymic and head and neck cancers.
Signed a Research Agreement with Merck & Co., Inc., (MSD) to conduct a preclinical research evaluation of dendrimer-based Antibody Drug Conjugates (ADCs) utilising Starpharma’s DEP
Signed and commenced a new DEP partnership with leading Chinese pharmaceutical company Chase Sun to develop several DEP nanoparticle formulations for an anti-infective drug.
Starpharma’s second radiopharmaceutical candidate, DEP HER2-lutetium, outperformed in a human breast cancer model.
Progressed development of several internal DEP candidates and programs, including DEP gemcitabine, DEP ADCs, and DEP radiopharmaceutical candidates for both therapeutic and diagnostic applications.
Starpharma continued to progress its undisclosed DEP partnered programs.
Developed and patented a DEP version of Gilead’s remdesivir (Veklury) with improved injection volume and pharmacokinetic characteristics.
Starpharma was invited to present its DEP technology at the prestigious, international Controlled Release Society (CRS) Virtual Annual Meeting, during a session called ‘Success Stories from Bench to Trials to Market’.
VivaGel Portfolio

VivaGel BV achieved TGA approval for an expansion of the marketing authorisation for VivaGel BV (Fleurstat BVgel) to include prevention of recurrent bacterial vaginosis – bringing the approved indications for VivaGel BV (Fleurstat BVgel) in line with those in Europe and Asia.
VivaGel BV was launched in the Nordic region, and new regulatory approvals were also received for countries in Africa and the Middle East, and further submissions were prepared.
In the US, a formal dispute resolution process is ongoing with the FDA as part of the regulatory process for VivaGel BV, and COVID-19 has had an impact on timing.
LifeStyles launched the VivaGel condom in countries in Europe, marketed under LifeStyles’ Manix and Akuel brands of condoms as the Absolute Dual Protection condom.
Corporate activities

Starpharma completed an oversubscribed A$48.9 million share placement and share purchase plan.
Starpharma concluded the year in a strong financial position with a cash balance of $60.5 million. Cash inflows from financing activities for the financial year include net proceeds of $46.9 million resulting from an equity placement and share purchase plan completed in September/October. Revenues for the year totalled $2.2 million, including $1.8 million for product sales, royalty, and research revenue from commercial partners, and interest income of $0.4 million. Other income of $1.3 million included $0.9 million of grant funding awarded by the Australian Government’s Medical Research Future Fund to expedite development and commercialisation of VIRALEZE. The net loss after tax for the year was $19.7 million, compared to $14.7 million last year. The key driver of this movement was the $4.4 million reduction in revenue in FY21 compared to the prior year due to the receipt of a US$3 million milestone payment from AstraZeneca in FY20. There was also a $1.1 million unfavourable unrealised foreign exchange movement (loss in FY21 of $0.8 million, gain in FY20 of $0.3 million) on foreign currencies held during FY21, compared to the prior corresponding period. Following the first launch of VIRALEZE in late March 2021, the product’s revenue for FY21 was $0.8 million. Starpharma originally supplied LloydsPharmacy with $1.4 million of VIRALEZE product, of which $0.7 million of revenue was not recognised for FY21 with stock returned following the temporary pause of sales and the likely repackaging requirements. Returned UK stock is scheduled to undergo repackaging shortly, incorporating a longer shelf-life as additional stability data is now available. This stock will then be made available for sale with the extended shelf-life.

Starpharma CEO, Dr Jackie Fairley, commented: "2021 has been a remarkable year for all of us around the world. Despite the impact of the unrelenting global pandemic, Starpharma was able to continue to recruit into our three DEP phase 2 clinical programs and achieve a number of important commercial milestones across the business. These included the rapid development and launch of VIRALEZE and the continued rollout of VivaGel products, as well as two new commercial DEP partnerships, and important progress for our three internal DEP phase 2 products. In parallel, we continued to build and advance new DEP assets into the preclinical pipeline in exciting and high-value areas like radiopharmaceuticals and Antibody Drug Conjugates (ADCs).

"It was fantastic to see our partner AstraZeneca expedite and expand its clinical program for their first DEP product, AZD0466, into a multi-region phase 1/2 study with the aim of facilitating marketing approvals as soon as possible. We also signed an exciting new partnership with leading global pharmaceutical company MSD (Merck & Co., Inc.) in the area of DEP ADCs, and progressed commercial discussions with potential partners for further potential DEP agreements. Internally, each of our three phase 2 clinical trials for DEP docetaxel, DEP cabazitaxel, and DEP irinotecan continued to recruit well despite the impact of COVID-19. We also developed further DEP assets, including DEP radiopharmaceutical candidates, into the preclinical pipeline".

Commenting on VIRALEZE, Dr Fairley said "The company is extremely proud to have developed, registered and launched VIRALEZE ahead of schedule and in time for it to play a role in the evolving situation in Europe. We were pleased to launch the product in the UK via LloydsPharmacy and online in other parts of Europe. VIRALEZE is now also registered in India and available online to consumers in multiple regions. Throughout the year, Starpharma continued to test SPL7013, the antiviral agent in VIRALEZE, against further respiratory viruses and new variants of SARS-CoV-2 as they emerged, with multiple laboratory studies showing that SPL7013 is virucidal, inactivating >99.9% against all four ‘Variants of Concern’, including the important Delta variant. The broad-spectrum activity of SPL7013 against multiple viruses and new variants is an important feature for the product, which demonstrates the potential further uses for VIRALEZE.

"In the year ahead, we will continue to advance our clinical DEP assets and expand our portfolio by progressing preclinical programs and leveraging Starpharma’s DEP platform to engage with new potential partners and increase market opportunities. The company also remains on track to progress further registrations, distribution arrangements and launches for VIRALEZE in other regions, while also supporting its partners to progress further registrations and launches of VivaGel products," concluded Dr Fairley.

Starpharma has published a standalone ESG (Environment, Social & Governance) Report which is available at View Source

Download ASX Announcement: Starpharma annual report and full year financial results (PDF, 5MB)

[1] Net cash burn is considered a non-IFRS value and has not been audited in accordance with Australian Accounting Standards. Net cash burn is calculated by the movement in cash and cash equivalents between reporting periods, adjusted for the impact of the capital raising during the period.

[2] Excluding the $46.9 million of equity raising net proceeds.

[3] SARS-CoV-2 is the virus that causes COVID-19.

On August 26, 2021 Adagene Inc. ("Adagene") (Nasdaq: ADAG), a platform-driven, clinical-stage biopharmaceutical company committed to transforming the discovery and development of novel antibody-based immunotherapies, reported financial results for the six months ended June 30, 2021, and provided corporate updates (Press release, Adagene, AUG 26, 2021, View Source [SID1234586930]).

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"During the first half of 2021, we advanced our clinical pipeline of three highly differentiated immuno-oncology candidates, while building a robust pipeline of novel preclinical programs that leverage our unique computational biology and artificial intelligence (AI) powered technology platforms," said Peter Luo, Ph.D., Co-founder, Chief Executive Officer and Chairman of Adagene. "With three Merck collaborations now in place, we’ve refined our global clinical development strategies to enhance efficiency and optimize our plans moving forward, while we anticipate key upcoming data from ongoing trials. Our pipeline aims to transform cancer therapy with the first of a new class of agonist antibodies targeting CD137, as well as new modalities and novel combinations to unlock the value of CTLA-4 as a proven target and the backbone of future immunotherapies. Applying our unique technology platforms and translational expertise, our goal is to strike a balance between safety and efficacy, addressing the core challenge of oncology drug development."

Recent Highlights and Upcoming Milestones

ADG106: This NEObody program is a fully human ligand-blocking, agonistic anti-CD137 IgG4 monoclonal antibody (mAb) that is being evaluated in patients with advanced solid tumors and/or non-Hodgkin’s lymphoma.

Evaluated ADG106 in 98 patients in phase 1 monotherapy dose escalation trials in U.S. (ADG106-1001) and China (ADG106-1002):
ADG106 monotherapy was well tolerated at doses of 3 mg/kg and 5 mg/kg. Limited treatment emergent adverse events were observed (i.e., limited liver toxicity or hematologic abnormalities). Results showed evidence of efficacy with a 56% disease control rate, and more than 30% tumor shrinkage was observed in 75% of patients with positive biomarker expression (via retrospective analysis), including a partial response evaluated by RECIST v1.1 in a patient with a solid tumor who failed multiple prior therapies.
Data from these trials were published at the ASCO (Free ASCO Whitepaper) 2021 Annual Meeting.
Continued dose escalation in a phase 1b/2 trial (ADG106-1008) evaluating safety and preliminary efficacy of ADG106 in combination with toripalimab, an approved anti-PD-1 in China. This trial is targeting biomarker-enriched tumors in patients who failed prior standard and/or immuno-oncology therapies.
Preliminary data from this trial demonstrate target engagement as shown by a dose-dependent pharmacodynamic biomarker, consistent with the monotherapy trials.
Implementing a biomarker-enriched tumor targeting strategy for a phase 1b/2 trial of ADG106 in combination with pembrolizumab (ADG106-P2001; KEYNOTE-D12) in the U.S. and Asia Pacific (APAC), integrating earlier plans for the ADG106-2001 trial. Data from this trial are expected in 2022.
Upcoming ADG106 milestones:
H2 2021
Results from ongoing trial in combination with toripalimab (ADG106-1008)
Complete patient follow up in monotherapy trials in the U.S. (ADG106-1001) and China (ADG106-1002)
2022
Results from combination trial with pembrolizumab (ADG106-P2001)
ADG116: This NEObody program, targeting a unique epitope of CTLA-4, is being evaluated in patients with advanced/metastatic solid tumors. ADG116 is designed to enhance efficacy by potent Treg depletion in the tumor microenvironment (TME) and to maintain its physiological function by soft ligand blocking in order to address safety concerns associated with existing CTLA-4 therapeutics.

Continued dose escalation in a global phase 1 clinical trial evaluating the safety and tolerability of ADG116 in patients with advanced/metastatic solid tumors (ADG116-1003):
ADG116 has shown no dose-limiting toxicities at doses up to 6 mg/kg, which is twice the 3 mg/kg dose level approved for the commercially available CTLA-4 therapy in specific indications. Dosing at 10 mg/kg is being initiated.
This trial is on track to be expanded this year with two combination cohorts investigating safety and preliminary efficacy of ADG116 with either toripalimab or ADG106 in patients with advanced/metastatic solid tumors, integrating earlier plans for the ADG106-1003 trial.
Obtained approval of Investigational New Drug application (IND) from China’s National Medical Products Administration (NMPA) for a phase 1 monotherapy trial in China (ADG116-1002).
On track to advance a phase 1 trial of ADG116 in combination with pembrolizumab (ADG116-P001; KEYNOTE C97) in the U.S. and APAC in 2022.
Upcoming ADG116 milestones:
H2 2021
Results from ongoing dose escalation of ADG-116 monotherapy (ADG116-1003)
2022
Results from ongoing dose escalation of combination cohorts, including the combination of ADG116 with toripalimab and ADG106 (ADG116-1003), respectively
Results from combination trial with pembrolizumab (ADG116-P001)
ADG126: The SAFEbody program targets CTLA-4 with a compelling preclinical profile and is designed to provide enhanced safety. ADG126 is designed for conditional activation in the TME, as well as to enhance efficacy by potent Treg depletion and to maintain its physiological function by soft ligand blocking in order to expand the therapeutic index and further address safety concerns with existing CTLA-4 therapies.

Continued dose escalation in a global phase 1 clinical trial evaluating the safety and tolerability of ADG126 in patients with advanced/metastatic solid tumors (ADG126-1001).
In April 2021, presented an update on preclinical data at the AACR (Free AACR Whitepaper) Annual Meeting. Preclinical data demonstrated ADG126 was well tolerated at doses up to 200 mg/kg, with an encouraging antitumor response in multiple immune-competent mouse tumor models in a dose-dependent manner both as a single agent and in combination with anti-PD-1 and other therapies.
Submitted IND to NMPA for a phase 1, dose-escalation and cohort expansion trial of ADG126 in China as monotherapy, and in combination with toripalimab, to evaluate safety and preliminary efficacy in patients with advanced/metastatic solid tumors (ADG126-1002).
On track to advance a phase 1 trial of ADG126 in combination with pembrolizumab (ADG126-P001; KEYNOTE-C98) in the U.S. and APAC in 2022.
Upcoming ADG126 milestones:
H2 2021
Results from ongoing dose escalation of ADG126 monotherapy (ADG126-1001)
2022
Results from dose escalation and cohort expansion of ADG126 (ADG126-1002)
Results from combination trial with pembrolizumab (ADG126-P001)
Preclinical Discovery Programs: The company continues to expand and advance a pipeline of innovative preclinical programs leveraging its NEObody, SAFEbody and/or POWERbody technologies to support the goal of submitting more than ten INDs or equivalent applications in the next three to five years.

Currently, five programs utilizing POWERbody and SAFEbody technologies are undergoing IND-enabling studies, including a highly differentiated anti-CD47 program, and bispecific T-cell engager programs that target both liquid and solid tumors.
All five programs have a robust Chemistry, Manufacturing and Controls (CMC) profile with encouraging preclinical safety and efficacy data.
Since March 31, 2021, the company has advanced two additional programs into CMC activity, further enhancing its portfolio of future IND candidates.
Upcoming preclinical discovery milestones:
2021
Continue advancement of multiple candidates undergoing IND-enabling studies
2022
Submission of multiple INDs or equivalent to advance innovative candidates from the company’s deep, broad, and differentiated preclinical discovery pipeline
Collaborations:

Established clinical trial collaboration and supply agreements with Merck for all three clinical candidates:
In July 2021, Adagene entered into two clinical collaborations with Merck, a leader in immuno-oncology. The collaborations include two open-label, dose escalation and expansion clinical studies to evaluate Adagene’s anti-CTLA-4 mAb product candidates, ADG116 and ADG126, in combination with pembrolizumab for patients with advanced/metastatic solid tumors, respectively.
In August 2021, Adagene entered into a third clinical collaboration with Merck to evaluate ADG106 in combination with pembrolizumab in advanced or metastatic solid and/or hematological malignancies.
Advanced the company’s ongoing collaboration with Guilin Sanjin Pharmaceutical Co., Ltd., or Sanjin, and its affiliates to develop two different monoclonal antibodies:
ADG104, an anti-PD-L1 monoclonal antibody, demonstrated promising data in ongoing phase 1b and phase 2 clinical trials concurrently in China. As of June 30, 2021, 4 patients had partial responses, 16 had stable disease, and a disease control rate of 50% was observed in 40 evaluable patients with various tumor types who received ADG104 monotherapy.
The second program, an anti-CSF-1R monoclonal antibody, received IND approval from the NMPA in March, and a phase 1 trial is expected to initiate dosing soon.
Corporate Updates

The company announced, effective immediately, a change in composition of the board of directors (the "Board") of Adagene Inc. Mr. Yu Miao, a director designated by JSR Limited pursuant to the current effective shareholders agreement, has resigned from the Board due to personal reasons. Mr. Miao confirms that he has no disagreement with the company. Adagene is appreciative of Mr. Miao for his service and valuable contributions to the Board.
The company has further strengthened its leadership team with recent hires across functions:
Steve Fischkoff, M.D., was appointed as interim Chief Medical Officer of Adagene. Dr. Fischkoff is a board-certified medical oncologist who has been active in the pharmaceutical industry for approximately 30 years. Previously, while at Medarex, Dr. Fischkoff led the clinical development of Yervoy (ipilumumab), the first checkpoint inhibitor and the only anti-CTLA-4 product approved by the U.S. Food and Drug Administration. He also served as the clinical lead from first-in-human through submission and approval in the U.S. and the EU of Humira (adalimumab), the world’s top selling pharmaceutical product, at Knoll Pharmaceuticals and Abbott Laboratories.
Jin Shang, Ph.D., was appointed as Senior Vice President of Global Regulatory Affairs. Dr. Shang brings more than 20 years of research, drug development and regulatory experience in the biopharmaceutical industry and most recently served as Director of Regulatory Affairs, Oncology at AstraZeneca, and previously held positions at Sun Pharma, Morphic Therapeutic, and Merck.
Wenlin Zeng, Ph.D., was appointed as Vice President of Cell Line and Upstream. Dr. Zeng will manage cell line and upstream process development, as well as oversee subsequent manufacturing of biological products. Dr Zeng brings more than 20 years of experience in cell line development, cGMP cell banking and drug substance manufacturing. She most recently served as Senior Director at Gilead and previously held positions at Forty-Seven, NGM Bio, Advanced Bioscience Laboratories, GlaxoSmithKline, MedImmune Vaccines, Abgenix and Scios.
Ami C. Knoefler was appointed as Vice President of Investor Relations and Corporate Communications. She has more than 25 years of global experience in pharmaceutical, biotech and medical technology communications. She most recently served as Senior Director at Ascendis Pharma, and previously held positions at Jazz Pharmaceuticals, PDL BioPharma, Abgenix and Bristol-Myers Squibb.
Expanded the Scientific and Strategic Advisory Board (SAB) to include pioneers in the immuno-oncology field: Steve Fischkoff, M.D., Stanley Frankel, M.D., FACP and Robert Spiegel, M.D., FACP. Adagene’s SAB is comprised of industry leaders who have played a key role in the field of immuno-oncology. The SAB will work cohesively with management and other key advisors to provide strategic input as the company pursues global clinical development of its transformative, expanding pipeline.
In July, Adagene authorized a share repurchase program under which the Company may repurchase up to US$20 million of its ordinary shares in the form of American depositary shares.
Financial Highlights

Cash and Cash Equivalents
Cash and cash equivalents were US$208.3 million as of June 30, 2021, compared to US$75.2 million as of December 31, 2020. The increase was mainly due to net proceeds of US$145.9 million from the company’s Initial Public Offering in February 2021. In addition, in March 2021, Adagene received US$11.0 million from Exelixis, Inc., as per the terms of the collaboration and license agreement.

Prepayments and Other Current Assets
Prepayments and other current assets were US$5.4 million as of June 30, 2021, compared to US$3.8 million as of December 31, 2020. The increase was driven by expanded R&D activities and associated advanced payments made.

Contract Liabilities
Contract liabilities were US$11.1 million as of June 30, 2021, compared to US$0.7 million as of December 31, 2020. The increase was due to the collaboration and license agreement signed with Exelixis as the related performance obligations have not been fulfilled.

Net Revenue
Net revenue was US$1.4 million for the six months ended June 30, 2021, compared to US$0.3 million for the same period in 2020. The increase was due to a payment of US$1.2 million from Dragon Boat Pharmaceuticals, a subsidiary of Sanjin, related to fulfillment of performance obligations associated with the companies’ collaboration to develop antibody-based therapies.

Research and Development Expenses
Research and development expenses were US$31.5 million for the six months ended June 30, 2021, compared to US$14.9 million for the same period in 2020. The increase was primarily attributable to an (i) increase in payroll and other related personnel costs by US$4.3 million due to headcount growth and average payroll increase in research and development, (ii) increase in non-cash share-based compensation expenses by US$3.1 million, and (iii) increase in costs related to preclinical testing and clinical trials due to progression of the programs and increased contract manufacturing costs by US$8.0 million. Adagene incurred US$16.6 million for project ADG106, ADG116 and ADG126 for the six months ended June 30, 2021, compared to US$13.0 million for the same period in 2020. Besides, Adagene incurred US$14.8 million for preclinical product candidates, research pipeline and others for the six months ended June 30, 2021, compared to US$1.9 million for the same period in 2020.

General and Administrative (G&A) Expenses
G&A expenses were US$7.4 million for the six months ended June 30, 2021, compared to US$4.7 million for the same period in 2020. The increase was primarily due to an (i) increase in headcount and average payroll and (ii) increase in professional fees and office expenses.

Net Loss
The net loss attributable to Adagene Inc.’s shareholders was US$37.2 million for the six months ended June 30, 2021, compared to US$18.2 million for the six months ended June 30, 2020.

Non-GAAP Net Loss
Non-GAAP net loss, which is defined as net loss attributable to ordinary shareholders for the period after excluding (i) share-based compensation expenses and (ii) accretion of convertible redeemable preferred shares to redemption value was US$27.0 million for the six months ended June 30, 2021, compared to US$11.1 million for the six months ended June 30, 2020. Please refer to the section in this press release titled "Reconciliation of GAAP and Non-GAAP Results" for details.

Non-GAAP Financial Measures

The Company uses non-GAAP net loss and non-GAAP net loss per ordinary shares for the year/period, which are non-GAAP financial measures, in evaluating its operating results and for financial and operational decision-making purposes. The Company believes that non-GAAP net loss and non-GAAP net loss per ordinary shares for the year/period help identify underlying trends in the Company’s business that could otherwise be distorted by the effect of certain expenses that the Company includes in its loss for the year/period. The Company believes that non-GAAP net loss and non-GAAP net loss per ordinary shares for the year/period provide useful information about its results of operations, enhances the overall understanding of its past performance and future prospects and allows for greater visibility with respect to key metrics used by its management in its financial and operational decision-making.

Non-GAAP net loss and non-GAAP net loss per ordinary shares for the year/period should not be considered in isolation or construed as an alternative to operating profit, loss for the year/period or any other measure of performance or as an indicator of its operating performance. Investors are encouraged to review non-GAAP net loss and non-GAAP net loss per ordinary shares for the year/period and the reconciliation to their most directly comparable GAAP measures. Non-GAAP net loss and non-GAAP net loss per ordinary shares for the year/period here may not be comparable to similarly titled measures presented by other companies. Other companies may calculate similarly titled measures differently, limiting their usefulness as comparative measures to the Company’s data. The Company encourages investors and others to review its financial information in its entirety and not rely on a single financial measure.

Non-GAAP net loss and non-GAAP net loss per ordinary shares for the year/period represent net loss attributable to ordinary shareholders for the year/period excluding (i) share-based compensation expenses, and (ii) accretion of convertible redeemable preferred shares to redemption value. Share-based compensation expense is a non-cash expense arising from the grant of stock-based awards to employees. The Company believes that the exclusion of share-based compensation expenses from the net loss in the Reconciliation of GAAP and Non-GAAP Results assists management and investors in making meaningful period-to-period comparisons in the Company’s operating performance or peer group comparisons because (i) the amount of share-based compensation expenses in any specific period may not directly correlate to the Company’s underlying performance, (ii) such expenses can vary significantly between periods as a result of the timing of grants of new stock-based awards, and (iii) other companies may use different forms of employee compensation or different valuation methodologies for their share-based compensation.

Please see the "Reconciliation of GAAP and Non-GAAP Results" included in this press release for a full reconciliation of non-GAAP net loss and non-GAAP net loss per ordinary shares for the year/period for the year/period to net loss attributable to ordinary shareholders for the year/period.

On August 26, 2021 Avalo Therapeutics, Inc. (Nasdaq: AVTX), a leading clinical-stage precision medicine company that discovers, develops, and commercializes targeted therapeutics for patients with significant unmet clinical need in immunology, immuno-oncology, and rare genetic diseases reported that it has launched its new corporate name Avalo Therapeutics, Inc (Press release, Cerecor, AUG 26, 2021, View Source [SID1234586929]). This new name reflects the Company’s dedication to helping address the significant unmet medical need for patients, as well as to align with the forward momentum of its large and promising pipeline of potential first-in-class therapeutic candidates. In conjunction with the corporate name change, the Company will trade on the Nasdaq Capital Market under the new ticker symbol "AVTX". The new ticker will become effective at the open of the market on August 26, 2021. In addition, the Company will launch a new website address: www.avalotherapeutics.com.

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"The rebranding from Cerecor to Avalo Therapeutics comes at a defining moment in our Company’s history and better reflects who we are today with our increased focus on immunology, immuno-oncology, and rare genetic diseases," said Michael F. Cola, President and Chief Executive Officer of Avalo Therapeutics. "We are excited to continue the advancement of our programs, including our recent expansion of AVTX-002, a promising first-in-class monoclonal antibody, into moderate-to-severe ulcerative colitis refractory to anti-TNF alpha therapies. As we enter this exciting period of our corporate journey, we look forward to the numerous data readouts in the second half the 2021."

Avalo Therapeutics Pipeline

The Company’s current pipeline consists of six product candidates advancing in development with eight ongoing clinical programs.

AVTX-002: Anti-LIGHT mAb targeting immune-inflammatory diseases including acute respiratory distress syndrome (ARDS) and moderate-to-severe inflammatory bowel disease (Crohn’s disease and ulcerative colitis)
AVTX-007: Anti-IL-18 mAb targeting immuno-oncology and immune-inflammatory diseases including multiple myeloma and Still’s disease
AVTX-006: A dual mTORc1/c2 inhibitor targeting complex lymphatic malformations. This product candidate currently has Orphan Drug and Rare Pediatric Disease Designation and is eligible for a Priority Review Voucher upon approval by the U.S. Food and Drug Administration (FDA).
AVTX 800 programs (AVTX-801, AVTX-802, and AVTX-803): Therapeutic doses of monosaccharide therapies for congenital disorders of glycosylation (CDGs). Each product candidate has Orphan Drug, Fast Track and Rare Pediatric Disease Designations and is eligible for a Priority Review Voucher upon approval by the U.S. FDA.

On August 26, 2021 Protalix BioTherapeutics, Inc. (NYSE American:PLX) (TASE:PLX), a biopharmaceutical company focused on the development, production and commercialization of recombinant therapeutic proteins produced by its proprietary ProCellEx plant cell-based protein expression system, reported that it has completed exchanges (the "Exchanges") of the Company’s outstanding 7.50% Senior Secured Convertible Notes due 2021 (the "2021 Notes") with institutional note holders of a substantial majority of the 2021 Notes (Press release, Protalix, AUG 26, 2021, View Source [SID1234586928]). Participating institutional note holders include funds managed by Highbridge Capital Management, LLC, UBS O’Connor LLC, Citigroup Global Markets, Whitebox Advisors and Tulip Capital.

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"The exchange of the notes will allow us to continue proceeding towards resubmission of PRX-102 BLA to the FDA subject to the outcome of the Type A meeting scheduled for September 9, 2021, as well as submission of the MAA to the EMA, subject to the meeting with the EMA scheduled for October 2021" said Dror Bashan, Protalix’s President and Chief Executive Officer. "We would like to thank the participants in the exchanges for their longstanding partnership."

The Exchanges, which were first announced on August 13, 2021, involved the exchange of an aggregate of $54.65 million principal amount of 2021 Notes for an aggregate of $28.75 million principal amount of newly issued 7.50% Senior Secured Convertible Notes due 2024 (the "Exchange Notes"), $25.90 million in cash and approximately $1.1 million in cash representing accrued and unpaid interest through the closing date. The initial conversion rate of the Exchange Notes is 563.2216 shares of the Company’s common stock (the "Common Stock") per $1,000 principal amount of Exchange Notes, which is equivalent to an initial conversion price of approximately $1.7755 per share of Common Stock, subject to adjustment in certain circumstances. This initial conversion price represents a premium of approximately 32.5% relative to the closing price of the Common Stock on the NYSE American on August 13, 2021. After giving effect to the Exchanges, $3.27 million aggregate principal amount of the Existing Notes are currently outstanding.

This announcement is neither an offer to sell nor a solicitation of an offer to buy any of these securities and does not constitute an offer, solicitation, or sale in any jurisdiction in which such offer, solicitation, or sale is unlawful. The offer and sale of the Exchange Notes and the shares of Common Stock issuable upon conversion of the Exchange Notes, if any, was not registered under the Securities Act of 1933 or any state securities laws, and unless so registered, the Exchange Notes and such shares may not be offered or sold in the United States except pursuant to an exemption from the registration requirements of the Securities Act of 1933 and applicable state laws.

On August 26, 2021 Molecular Partners Reported that Corporate Highlights and Key Financials for H1 2021 (Press release, Molecular Partners, AUG 26, 2021, View Source [SID1234586927])

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

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Research & Development:

Initiated two global Phase 2 and 3 trials of ensovibep (MP0420), to explore safety and efficacy in ambulatory patients with COVID-19 (EMPATHY) in collaboration with Novartis, and hospitalized patients (ACTIV-3) sponsored by the National Institutes of Health (NIH)
Received FDA Fast Track designation for ensovibep for the treatment of COVID-19 in both hospitalized and ambulatory settings
Initiated and fully enrolled Phase 2a single arm study of ensovibep in the Netherlands in patients with mildly symptomatic COVID-19, with data expected to be presented in a scientific conference in H2 2021
Reported that in vitro studies indicate that ensovibep maintains potency against all known SARS-CoV-2 variants of concern, including Delta and Lambda
Presented data further supporting the MP0317, T-cell engager, and Peptide-MHC oncology programs at AACR (Free AACR Whitepaper)
In August, announced receipt of global rights of abicipar pegol for the treatment of neovascular AMD (nAMD) and Diabetic Macular Edema, following termination of license and collaboration agreement by AbbVie Inc.
Leadership & Governance:

Elected Agnete Fredriksen and Dominik Höchli to the Board of Directors at the Annual General Meeting of April 21, 2021
Financial highlights:

Successfully completed initial public offering of American Depositary Shares ("ADSs") on the Nasdaq, raising $63.8 million (CHF 58.8 million) in gross proceeds to support ongoing operations into H2 2023
Ongoing strong financial position with CHF 174.3 million in cash and short-term deposits as of June 30, 2021
Net cash outflow from operating activities of CHF 52.5 million in H1 2021
FY 2021 expense guidance maintained at CHF 65-75 million
ZURICH, Switzerland, Aug. 26, 2021 (GLOBE NEWSWIRE) — Ad hoc announcement pursuant to Art. 53 LR
Molecular Partners AG (SIX: MOLN, NASDAQ: MOLN), a clinical-stage biotech company developing a new class of custom-built proteins known as DARPin therapeutics, reported its corporate highlights and unaudited financial results for the first half-year of 2021.

"Molecular Partners strongly expanded our global clinical presence and collaboration with Novartis in the first half of the year as the evolving COVID-19 pandemic continued to underscore the need for effective antiviral therapeutics. As a now dual-listed company in Switzerland and the United States, our expanded investor base enables us to accelerate our mission to deliver a new class of medicines to people living with cancer and infectious diseases," said Patrick Amstutz, Ph.D., Chief Executive Officer of Molecular Partners. "To have entered two ongoing, late-stage trials of ensovibep further illustrates our rapid design and development capabilities. In addition to the COVID-19 program we are focused on expanding into new antiviral applications of the DARPin platform while moving towards a new phase for our immuno-oncology programs."

Antiviral program: Rapid development of trispecific antiviral DARPin candidate ensovibep in multiple international clinical trials

Molecular Partners advanced in 2021 with strong momentum for the Company’s lead antiviral candidate, ensovibep, which has progressed in the second quarter of 2021 into two ongoing, late-stage global clinical studies, EMPATHY and ACTIV-3, in collaboration with Novartis and the NIH, respectively. Thus far, ensovibep has provided positive Phase 1 data and continued to maintain potency in laboratory studies against all known COVID-19 variants of concern.

In March of 2021, Molecular Partners and its collaboration partner Novartis announced that the National Institutes of Health (NIH) selected ensovibep for inclusion in a global phase 3 randomized, controlled clinical trial as part of NIH’s Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) program. The international master protocol ACTIV-3 is designed to evaluate the safety and efficacy of various therapies for the treatment of adults hospitalized with a COVID-19 diagnosis. A sub-study of ACTIV-3 evaluating ensovibep began enrolling hospitalized patients in June 2021 and is currently enrolling patients across seven countries. Topline data from this study are expected in 2022.

In May of 2021, Molecular Partners and its collaboration partner Novartis announced the start of the clinical trial EMPATHY, a global phase 2 – 3 study, to explore the use of ensovibep for the treatment of COVID-19 in patients who are in the early stages of infection, to prevent worsening symptoms and hospitalization. Molecular Partners’ collaboration partner Novartis is conducting the clinical trial for ensovibep, with Molecular Partners as sponsor. EMPATHY is currently enrolling patients across five countries. Topline interim data for the first 400 patients are expected towards the end of second half of 2021with complete data expected in 2022.

In April of 2021, the first patient was dosed in a Phase 2a clinical trial of ensovibep in a single arm, open label study in the Netherlands that enrolled patients with mild symptomatic COVID-19, and is designed to evaluate the dynamics of viral clearance, pharmacokinetics and tolerability of ensovibep. This study enrolled a total of 12 patients in two dose cohorts, with data expected to be presented in a scientific conference in H2 2021. Initial results show a steady decline of viral loads in treated patients, validating the follow-up methods implemented in the Company’s ongoing late-stage trials, EMPATHY and ACTIV-3.

In March 2021, Molecular Partners reported positive initial Phase 1 results in healthy volunteers. Ensovibep, administered intravenously (I.V.), was seen to be safe and well tolerated, with no serious or severe adverse events reported. These preliminary results also confirmed extended exposure to ensovibep in serum, with a half-life of 2-3 weeks, as was expected from preclinical experiments. These data confirmed the systemic administration of ensovibep to be safe and well tolerated and supported the initiation of later stage trials. Following I.V. administration, ensovibep was also evaluated for safety and half-life when administered in bolus, and is presently being evaluated in subcutaneous (S.C.) administration in healthy subjects.

DARPin molecules offer a differentiated approach to treating COVID-19 through a ‘cocktail in a molecule’ mechanism; a single molecule that can engage three domains of the SARS-CoV-2 virus simultaneously to inhibit viral entry into cells. This allows for a potentially broader efficacy and reduces the likelihood for the development of viral drug resistance which can result from selection pressure on any single molecular target. In addition, DARPin candidates are produced through rapid, high-yield microbial fermentation for potential speed and logistical advantages over mammalian cell production employed for antibodies.

Based on the success seen to-date of ensovibep’s unique approach to neutralizing the virus, Molecular Partners is also evaluating the next generation of opportunities to develop antivirals against other infectious diseases with global unmet need.

Immuno-oncology programs: Clinical work for AMG 506 / MP0310 (FAP x 4-1BB) ongoing; new supportive data published across acute myeloid leukemia and MP0317 (FAP x CD40) programs as well as novel technology platforms

Following the positive initial results of MP0310, clinical work advanced into weekly administration of MP0310 in the Phase 1 study, to identify a dosing regimen to obtain sustained 4-1bb activation. Molecular Partners expects to obtain data from this trial within 2021, allowing for its partner, Amgen, to evaluate potential future development of MP0310 in combination with Amgen’s oncology assets, including BiTE molecules.

In April of 2021, Molecular Partners presented four posters highlighting research across its immuno-oncology programs at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) virtual Annual Meeting. Molecular Partners’ novel multi-specific DARPin candidates are designed to activate the immune system to fight cancer while reducing damage to healthy cells. These candidates use multiple novel DARPin technologies potentially applicable against a wide range of tumor types. The preclinical data shared include first results from the Company’s acute myeloid leukemia (AML) CD3 T-cell engager program, initial results from the CD3 prodrug program, and new data from the MP0317 and peptide-MHC programs.

With respect to MP0317, a multi-specific DARPin product candidate targeting both FAP and CD40 to enable tumor-localized immune activation, new preclinical data showed activation of B-cells and myeloid cells in ex vivo human tumor samples. This demonstrated that physiological presence of FAP, expressed in the connective tissue of a broad range of solid tumors, is mandatory and sufficient for MP0317 to induce immune activation. Furthermore, the data presented at AACR (Free AACR Whitepaper) shows that MP0317 led to a range of pro-inflammatory activities, including macrophage repolarization and reversion of T‑cell suppression only in the presence of FAP. In both assays the killing effect was comparable to that achieved by an anti-CD40 antibody. The Company believes these data support MP0317’s potential to deliver tumor-localized CD40-mediated immune cell activation while avoiding systemic toxicity seen with other agents. MP0317 is anticipated to begin clinical trials in the second half of 2021.

In preclinical studies, the Company’s AML research candidates demonstrated substantial activity against different populations of AML cells in vitro and ex vivo, without significant damage to healthy cells. The candidate is further designed to bind with increased avidity as the number of relevant antigens presented increases, further strengthening its preference for tumor cells. The candidate is a single molecule designed to target three different cancer antigens simultaneously (CD70, CD33, and CD123). This multi-specific DARPin T-cell engager candidate is designed to deliver a highly potent and specific anti-tumor response to AML cells, with a reduced effect on healthy normal cells, and with the potential to counteract target escape mechanisms expected due to tumor heterogeneity. The AML DARPin candidate demonstrated potent induction of T-cell mediated cytotoxicity against AML cell lines and primary AML calls. In an ex vivo assay using fresh blood from healthy donors, the candidate induced profoundly less inflammatory cytokine production and reduction in platelet counts than T-cell engager candidates in development by other parties. Molecular Partners believes this candidate shows a unique avidity-driven ability to kill a broader population of AML cells while decreasing the risk of toxicity.

Molecular Partners’ T-cell engager programs also include a novel prodrug DARPin technology for tumor-localized release of immune stimulation, through incorporation of a protease-cleavable blocker DARPin molecule. As CD3-binding T-cell engagers are highly potent and can lead to systemic toxicities, Molecular Partners has developed a DARPin domain designed to mask the CD3 engager from interacting with T cells, systemically or outside of the tumor, thus reducing toxicity by limiting immune activation to the tumor microenvironment. Molecular Partners’ prodrug research candidate, CD3-PDD, has demonstrated in vitro and in vivo proof-of-concept, being shown to be unable to bind and recruit T-cells in its non-cleaved state in circulation while delivering an anti-tumor effect.

Finally, new data were presented supporting Molecular Partners’ peptide-MHC targeting program, which focuses on developing the capability to target cell surface protein complexes indicating disease through display of intracellular peptides. At AACR (Free AACR Whitepaper), the Company presented preclinical results demonstrating rapid and reliable generation of DARPin proteins against a peptide-MHC complex (pMHC). These DARPin proteins were then formatted into bispecific T-cell engagers, and engineered to enable potent and specific activation of T cells. Further, the results showed that a pMHC-targeting DARPin candidate was able to achieve systemic half-life extension.

Ophthalmology

In August, the Company was updated by its collaboration partner, AbbVie Inc. of its termination of the license and collaboration agreement for the investigational drug abicipar pegol for the treatment of nAMD and DME. As such, Molecular Partners will regain the development and commercial rights of abicipar on a worldwide basis.

Financial Highlights: Nasdaq offering extends cash runway into H2 2023

Molecular Partners remains solidly funded to capture upcoming value inflection points. In June 2021, the Company successfully completed an initial public offering of American Depositary Shares on the NASDAQ exchange, raising $63.8 million (CHF 58.8 million) in gross proceeds. With the U.S. listing, Molecular Partners has broadened its access to capital from the global investment community to support its programs and growing pipeline. In the first six months of 2021, Molecular Partners recognized total revenues and other income of CHF 4.4 million (H1 2020: CHF 7.5 million) and incurred total operating expenses of CHF 39.2 million (H1 2020: CHF 30.6 million). This led to an operating loss of CHF 34.8 million for the first six months in 2021 (H1 2020: Operating loss of CHF 23.1 million) and a net loss of CHF 33.6 million for H1 2021 (H1 2020: Net loss of CHF 24.7 million).

The net cash outflow from operating activities during the first six months in 2021 was CHF 52.5 million (2020: net cash outflow of CHF 27.9 million). Including time deposits, the cash and cash equivalents position increased by CHF 0.6 million vs. year-end 2020 to CHF 174.3 million as of June 30, 2021 (December 31, 2020: CHF 173.7 million).

Total shareholders’ equity stood at CHF 134.6 million as of June 30, 2021, an increase of CHF 27.4 million (December 31, 2020: CHF 107.2 million). As of June 30, 2021, the Company employed 158 FTEs (full time equivalents), up 15 year-on-year. About 80% of the employees are employed in R&D-related functions.

BUSINESS OUTLOOK AND PRIORITIES
In the second half of 2021, Molecular Partners remains focused on the rapid clinical development of ensovibep across two major global studies as well as a further bridging study to evaluate the option of subcutaneous/intramuscular administration. Topline interim data for the first 400 patients from the ongoing EMPATHY trial are expected in the second half of 2021 with full interim data expected in early 2022. Molecular Partners is committed to advancing other antiviral programs and is currently evaluating several potential targets with global unmet need. The Company expects to announce additional antiviral programs in the second half of 2021. In immuno-oncology, Molecular Partners expects to provide results from the MP0310 trial to Amgen, to inform their decision regarding future development of the program. Further, the Company intends to begin clinical studies of MP0317 in the second half of 2021 and expects to present additional research data from its trispecific CD3 T-cell engager for the treatment of AML. Molecular Partners is now working with AbbVie for the receipt of data and materials related to the abicipar program. The Company has formed a special committee to evaluate the program and determine appropriate next steps regarding abicipar.

FINANCIAL OUTLOOK 2021

For the full year 2021, at constant exchange rates, the company continues to expect total expenses of CHF 65-75 million, of which around CHF 7 million will be non-cash effective costs.

In terms of cash outflow the company expects a gross cash utilization of CHF 85-95 million for FY2021, which includes a total of CHF 20 million payable to Novartis for the manufacturing of commercial supply (of which CHF 10.5 million occurred during H1 2021). This cash flow guidance does not include any potential receipts from R&D partnerships.

With CHF 174.3 million cash at hand and no debt as per June 30, 2021 the company expects to be funded into H2 2023, excluding any potential receipts from R&D partners.

DOCUMENTATION

The results presentation, this press release, and the half-year 2021 report will be made available on www.molecularpartners.com after 7:00am (CET) on August 26, 2021.

H1 2021 CONFERENCE CALL & AUDIO WEBCAST

Molecular Partners will hold a conference call and audio webcast on August 26, 2021, 2:00pm CET (1:00pm GMT, 8:00am EST).

In order to register for the H1 2021 conference call, please dial the following numbers approximately 10 minutes before the start of the presentation:

Participants in the conference call will have the opportunity to ask questions after the presentation.

AUDIO WEBCAST

The H1 2021 results presentation will be webcast live and will be made available on the Company’s website under the investor section. The replay will be available for 90 days following the presentation.

FINANCIAL CALENDAR

October 28, 2021 Interim Management Statement Q3 2021
December 13, 2021 R&D Day in New York
The latest timing of the above events can always be viewed on the investor section of the website.

ABOUT DARPin THERAPEUTICS

DARPin therapeutics are a new class of custom-built protein therapeutics based on natural binding proteins that open a new dimension of multi-functionality and multi-target specificity in drug design. A single DARPin candidate can engage more than five targets, and its flexible architecture and small size offer benefits over conventional monoclonal antibodies or other currently available protein therapeutics. DARPin therapeutics have been clinically validated through to the registrational stage. The DARPin platform is a fast and cost-effective drug discovery engine, producing drug candidates with optimized properties for development and very high production yields. DARPin is a registered trademark owned by Molecular Partners AG.