On August 28, 2022 Atomwise, an artificial intelligence–based drug discovery firm, reported that it has formed a research pact with Sanofi in which the partners will use Atomwise’s AtomNet computational platform on up to five drug targets (Press release, Atomwise, AUG 28, 2022, View Source [SID1234618859]). Sanofi will pay Atomwise $20 million, plus possible milestones, to identify, synthesize, and advance small molecules that will be exclusive to Sanofi. Atomwise’s platform employs AI algorithms for structure-based drug design and to search its virtual library of more than 3 trillion compounds that can be synthesized.

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On August 27, 2022 The Janssen Pharmaceutical Companies of Johnson & Johnson reported the final results from the randomized Phase 2 GRIFFIN study evaluating the investigational use of DARZALEX (daratumumab) in combination with lenalidomide (Revlimid), bortezomib (VELCADE) and dexamethasone (DARZALEX-RVd), followed by maintenance therapy with DARZALEX-lenalidomide (R), compared to RVd followed by maintenance therapy with R alone, in patients with newly diagnosed, transplant-eligible multiple myeloma (Press release, Johnson & Johnson, AUG 27, 2022, View Source [SID1234618717]). Data were presented in the plenary session at the 19th International Myeloma Society (IMS) Annual Meeting.

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In the primary analysis (median follow-up of 13.5 months), the GRIFFIN study met its primary endpoint, resulting in a higher stringent complete response (sCR) rate for DARZALEX-RVd compared with RVd alone by the end of post-autologous stem cell transplant (ASCT) consolidation therapy (42.4 percent vs. 32 percent; 1-sided P=0.0680) meeting the prespecified 1-sided alpha of 0.1. At IMS, the predefined final analysis for GRIFFIN (median follow-up of 49.6 months), which occurred after all patients had completed at least one year of follow-up after end of study therapy or withdrew, showed that longer progression-free survival (PFS) was observed in patients who received DARZALEX-RVd/DARZALEX-R compared to those who received RVd/R (hazard ratio = 0.45; 95 percent confidence interval, 0.21-0.95; P=0.0324).1 Higher minimal residual disease (MRD) negativity rates were observed for DARZALEX-RVd vs. RVd (64 percent vs. 30 percent). No new safety concerns were observed with longer-term follow-up.

"The final analysis of the GRIFFIN trial highlights the potential benefit of adding daratumumab to RVd for the treatment of newly diagnosed, transplant-eligible patients," said Douglas W. Sborov†, M.D., M.S., Director of the Multiple Myeloma Program at the Huntsman Cancer Institute at the University of Utah and GRIFFIN study investigator. "We are constantly investigating the role of new regimens and combinations to improve outcomes in our patients and GRIFFIN is another important step forward in this research."

Final Analysis from GRIFFIN

After two years of maintenance therapy, the MRD negativity rate continued to favor DARZALEX-RVd versus RVd (64 percent vs. 30 percent; P=<0.0001). Additionally, 44 percent of patients who received DARZALEX-RVd achieved sustained MRD negativity lasting 12 months or more, compared to 14 percent of patients in the RVd arm. Treatment with DARZALEX-RVd also resulted in higher sCR rates at all time points in the study, with the highest rates occurring following two years of maintenance therapy (67 percent vs. 48 percent; P=0.0079, respectively). CR or better rate was 83 percent in the DARZALEX-RVd arm vs. 60 percent in the RVd arm (P=0.005).

At the conclusion of the final analysis, after a median follow-up of 49.6 months, a 55 percent reduction in the risk of disease progression or death was observed in patients in the DARZALEX-RVd arm; an estimated 48-month PFS rate of 87.2 percent was observed in the DARZALEX-RVd arm, compared to 70 percent in the RVd arm. Median PFS was not reached in either treatment arm. In addition, after extended follow-up, no new safety concerns were observed.

"The Phase 2 GRIFFIN study showed important results with the investigational DARZALEX quadruplet regimen in the treatment of newly diagnosed, transplant-eligible multiple myeloma," said Imran Khan, M.D., Ph.D., U.S. Vice President, Medical Affairs, Hematology at Janssen Scientific Affairs, LLC. "The evaluation of this treatment regimen will continue as part of the registrational, Phase 3 PERSEUS study. These studies represent our ongoing focus in multiple myeloma and our commitment to advance research and new therapeutic combinations for patients at each stage of their treatment journey."

About the GRIFFIN Study

The Phase 2 GRIFFIN (NCT02874742) study evaluated the investigational regimen of DARZALEX in combination with RVd and enrolled and treated more than 200 adults ages 18-70 years with newly diagnosed multiple myeloma who were eligible for ASCT.

In the safety run-in cohort, 16 patients received 25 mg of lenalidomide orally on days 1-14; 1.3 mg/m2 of bortezomib subcutaneously on days 1, 4, 8 and 11; and 20 mg of dexamethasone on days 1, 2, 8, 9, 15 and 16, and every 21 days during the induction and consolidation phases (cycles 1-6). DARZALEX 16 mg/kg IV was given on days 1, 8 and 15 of cycles 1-4 and on day 1 of cycles 5-6.

During the maintenance phase (cycles 7-32), patients received 10 mg daily of lenalidomide (15 mg beginning at cycle 10 if tolerated) on days 1-21 every 28 days and DARZALEX 16 mg/kg IV every 56 days; this was amended to every 28 days based upon emerging clinical pharmacokinetic data demonstrating improved target saturation with every-4-week maintenance dosing. Maintenance therapy with lenalidomide could be continued beyond cycle 32, per local standard of care.

In the subsequent randomized Phase 2 portion of the study, 207 patients were randomized to treatment with RVd induction and consolidation, ASCT, and maintenance therapy with lenalidomide; or DARZALEX-RVd, ASCT, and maintenance therapy with DARZALEX and lenalidomide.

Janssen’s clinical development program continues to evaluate the potential of DARZALEX-containing quadruplet regimens in improving clinical outcomes for patients.

About DARZALEX

Janssen is committed to exploring the potential of DARZALEX (daratumumab) for patients with multiple myeloma across the spectrum of the disease. DARZALEX has been approved in eight indications, three of which are in the frontline setting, including newly diagnosed patients who are transplant eligible and ineligible.2

In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive license to develop, manufacture and commercialize daratumumab. DARZALEX has become a backbone therapy in the treatment of multiple myeloma, having been used in the treatment of more than 300,000 patients worldwide and more than 68,000 patients in the U.S. alone since its U.S. FDA approval in 2015.3 DARZALEX is the first CD38-directed antibody approved globally to treat multiple myeloma.5

CD38 is a surface protein that is present in high numbers on multiple myeloma cells, regardless of the stage of disease.4 DARZALEX binds to CD38 and inhibits tumor cell growth, causing myeloma cell death.4 DARZALEX may also have an effect on normal cells.4 Data across eight Phase 3 clinical trials, in both the frontline and relapsed settings, have shown that DARZALEX-based regimens resulted in significant improvement in PFS and/or OS.5,6,7,8,9,10,11,12

About Multiple Myeloma

Multiple myeloma is an incurable blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.2,3 When damaged, these plasma cells rapidly spread and replace normal cells with tumors in the bone marrow. In 2022, it is estimated that more than 34,000 people will be diagnosed and close to 12,000 will die from the disease in the U.S.13 While some patients with multiple myeloma have no symptoms, most patients are diagnosed due to symptoms, which can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems or infections.4

INDICATIONS

DARZALEX (daratumumab) is indicated for the treatment of adult patients with multiple myeloma:

In combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy
In combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant
In combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant
In combination with bortezomib and dexamethasone in patients who have received at least one prior therapy
In combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy
In combination with pomalidomide and dexamethasone in patients who have received at least two prior therapies including lenalidomide and a proteasome inhibitor
As monotherapy in patients who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent
IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

DARZALEX is contraindicated in patients with a history of severe hypersensitivity (eg, anaphylactic reactions) to daratumumab or any of the components of the formulation.

WARNINGS AND PRECAUTIONS

Infusion-Related Reactions

DARZALEX can cause severe and/or serious infusion-related reactions including anaphylactic reactions. These reactions can be life–threatening, and fatal outcomes have been reported. In clinical trials (monotherapy and combination: N=2066), infusion-related reactions occurred in 37% of patients with the Week 1 (16 mg/kg) infusion, 2% with the Week 2 infusion, and cumulatively 6% with subsequent infusions. Less than 1% of patients had a Grade 3/4 infusion-related reaction at Week 2 or subsequent infusions. The median time to onset was 1.5 hours (range: 0 to 73 hours). Nearly all reactions occurred during infusion or within 4 hours of completing DARZALEX. Severe reactions have occurred, including bronchospasm, hypoxia, dyspnea, hypertension, tachycardia, headache, laryngeal edema, pulmonary edema, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Signs and symptoms may include respiratory symptoms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting, and nausea. Less common signs and symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, hypotension and blurred vision.

When DARZALEX dosing was interrupted in the setting of ASCT (CASSIOPEIA) for a median of 3.75 months (range: 2.4 to 6.9 months), upon re-initiation of DARZALEX, the incidence of infusion-related reactions was 11% for the first infusion following ASCT. Infusion-related reactions occurring at re-initiation of DARZALEX following ASCT were consistent in terms of symptoms and severity (Grade 3 or 4: <1%) with those reported in previous studies at Week 2 or subsequent infusions. In EQUULEUS, patients receiving combination treatment (n=97) were administered the first 16 mg/kg dose at Week 1 split over two days, ie, 8 mg/kg on Day 1 and Day 2, respectively. The incidence of any grade infusion-related reactions was 42%, with 36% of patients experiencing infusion-related reactions on Day 1 of Week 1, 4% on Day 2 of Week 1, and 8% with subsequent infusions.

Pre-medicate patients with antihistamines, antipyretics, and corticosteroids. Frequently monitor patients during the entire infusion. Interrupt DARZALEX infusion for reactions of any severity and institute medical management as needed. Permanently discontinue DARZALEX therapy if an anaphylactic reaction or life-threatening (Grade 4) reaction occurs and institute appropriate emergency care. For patients with Grade 1, 2, or 3 reactions, reduce the infusion rate when re-starting the infusion.

To reduce the risk of delayed infusion-related reactions, administer oral corticosteroids to all patients following DARZALEX infusions. Patients with a history of chronic obstructive pulmonary disease may require additional post-infusion medications to manage respiratory complications. Consider prescribing short- and long-acting bronchodilators and inhaled corticosteroids for patients with chronic obstructive pulmonary disease.

Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with DARZALEX infusion. If ocular symptoms occur, interrupt DARZALEX infusion and seek immediate ophthalmologic evaluation prior to restarting DARZALEX.

Interference With Serological Testing

Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab infusion. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient’s serum. The determination of a patient’s ABO and Rh blood type is not impacted. Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX. Type and screen patients prior to starting DARZALEX.

Neutropenia and Thrombocytopenia

DARZALEX may increase neutropenia and thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX until recovery of neutrophils or for recovery of platelets.

Interference With Determination of Complete Response

Daratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some patients with IgG kappa myeloma protein.

Embryo-Fetal Toxicity

Based on the mechanism of action, DARZALEX can cause fetal harm when administered to a pregnant woman. DARZALEX may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX and for 3 months after the last dose.

The combination of DARZALEX with lenalidomide, pomalidomide, or thalidomide is contraindicated in pregnant women because lenalidomide, pomalidomide, and thalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, pomalidomide, or thalidomide prescribing information on use during pregnancy.

ADVERSE REACTIONS

The most frequently reported adverse reactions (incidence ≥20%) were upper respiratory infection, neutropenia, infusion–related reactions, thrombocytopenia, diarrhea, constipation, anemia, peripheral sensory neuropathy, fatigue, peripheral edema, nausea, cough, pyrexia, dyspnea, and asthenia. The most common hematologic laboratory abnormalities (≥40%) with DARZALEX are neutropenia, lymphopenia, thrombocytopenia, leukopenia, and anemia .

On August 27, 2022 Sanyou Biopharmaceuticals (Shanghai) Co., Ltd. (Sanyou) and Shanghai KangaBio Co., Ltd. (KangaBio) reported that they have reached an antibody drug licensing agreement, regarding a proprietary monoclonal antibody drug developed by Sanyou, which grants KangaBio an exclusive license to exploit the antibody for research, development, manufacturing and commercialization of immunotherapy products (Press release, Sanyou Biopharmaceuticals, AUG 27, 2022, View Source [SID1234618716]). KangaBio, as a rising star biotechnology company, is committed to developing innovative prodrugs and providing innovative medicine to address unmet clinical needs. While Sanyou is a biological high-tech company focusing on innovative antibody drugs R&D services. Based on the two companies’ respective strengths and industry resources, Sanyou and KangaBio will work together to contribute to the development of innovative prodrugs for immunotherapy.

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Previously, KangaBio and Sanyou reached a collaboration agreement on two monoclonal antibody drugs developed by Sanyou and signed high-level term sheet. In addition to the license transfer of drug candidates, the two companies have also successively reached to collaborative development, commissioned R&D, technical services and other forms of staged R&D collaboration. Sanyou fully exploits its 6 types of one-stop innovative antibody drug integrated services, 11 types of flexible and adaptable antibody drug R&D staged technical services and 11 types of diverse antibody generation featured services to fully support the drug development of KangaBio.

Dr. Weidong Jiang, founder and CEO of KangaBio, said, "We are looking forward to this collaboration. KangaBio is committed to developing low toxicity and high efficacy immuno-agonists and innovative prodrugs of multi-specific antibodies. This strategic partnership with Sanyou is expected to utilize the advantages of Sanyou’s internationally leading innovative antibody drug development and value transformation platform, to further enrich KangaBio’s innovative product pipeline, to accelerate the R&D of our innovative antibody drugs and to address unmet clinical needs."

Dr. Guojun Lang, founder and CEO of Sanyou, said, " We are extremely honored to collaborate with KangaBio again. During the past numerous collaborations, Sanyou has saved valuable time with the pre-clinical drug R&D for KangaBio, owing to the comprehensive innovative drug development system and rich industrialization experiences. The close collaboration also demonstrates the strong complementary character of our business layout. We look forward to more in-depth communication and collaboration with KangaBio in the future and wish that this collaboration will bring benefits to the development of KangaBio. Sanyou and Kanga will team up to accomplish remarkable achievements.

On August 26, 2022 The fiscal year 2021/2022 of Hamlet Pharma AB reported that it has been very successful and important milestones have been reached. The company has consolidated its financial position by raising significant capital, competed successfully for continued funding from the EU Horizon 2020 program, produced drug for clinical trials on a large scale, conducted successful clinical trials, added brain tumor therapy as a new indication for drug development and progressed with the BAMLET drug candidate (Press release, HAMLET Pharma, AUG 26, 2022, View Source;utm_medium=rss&utm_campaign=q4-year-end-report-july-2021-june-2022 [SID1234623366]).

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Financing and leadership

The year started with the successful completion of a funding round through a rights issue that provided the company with approximately 50.4 million SEK, before deductions for issue costs. Hamlet Pharma’s rights issue was oversubscribed by 260% for the B units. The company later received approximately SEK 5.8 million for warrants of series TO 3 B.

During the past year Hamlet Pharma received additional financial support from the EIC Accelerator Horizon 2020 fund. The European Union extended the funding after a successful 18-month report. The evaluators concluded that the company had "fully achieved the objectives and milestones for the period" and "remains in line with the objectives". The EU evaluators also noted that these advances were made despite the COVID pandemic, which seriously delayed many companies.

On the 1st of June 2022, Martin Erixon joined Hamlet Pharma as CEO. Martin Erixon combines a scientific background with extensive experience from major corporations. The former CEO Mats Persson will stay on as a senior advisor.

Clinical trial program

The clinical study in patients with bladder cancer continues according to plan. Significantly stronger effects were detected with a higher dose in the dose-escalation part of the study. The tumors were strongly affected in patients treated with five times higher amounts of Alpha1H, without an increase in side effects. Extensive molecular evaluation of the tumor response shows very encouraging results for the continued clinical trial program. Experienced consultant organizations are engaged in the discussions with the European and US regulatory authorities (EMA and FDA).

Hamlet Pharma’s strategy is to broaden the use of Alpha1H for other cancer indications, where tests in animal models already support therapeutic effects. To explore Alpha1H as brain tumor therapy, a collaboration agreement has been signed with a key opinion leader in the field of neurosurgery, Professor Steven Gill at the university of Bristol. Together with Neurochase Limited, founded by Steven Gill, Hamlet Pharma will develop a novel drug delivery technology and methods to treat tumors in the central nervous system with Alpha1H. The goal is to provide adequate materials and data to prepare for clinical trial applications.

Securing Alpha1H production for clinical studies

The external manufacturing partnerships for drug production include the synthesis of the Alpha1 peptide, the formulation of drug substance and clinical supply chain. Drug manufacturing has been successfully transferred to a new multinational commercial partner. During the third quarter, a new batch of Alpha1H was produced and shown to be stable and fully active against cancer cells, securing material for the continued clinical studies in patients with bladder cancer, which we regard as our highest priority.

Business development strategy

Hamlet Pharma and its network of pharmaceutical experts have established an interesting model for effective drug development with an emphasis on problem solving and minimizing risk. Hamlet Pharma has effectively delivered on its promises including positive clinical results and a dynamic technology platform. Hamlet Pharma was one of the few companies in the EU Horizon 2020 program to reach the promised milestones despite the Corona pandemic.

We are grateful for all efforts made by the teams in Sweden and Prague, the invaluable assistance from our committed consultants and for continued confidence and support from our shareholders.

Catharina Svanborg and Martin Erixon

Chairperson of the Board and CMO, and CEO, respectively, of Hamlet Pharma AB

Significant events during the fiscal year

Q1

On July 5, 2021, the Prospect defining Hamlet Pharma’s rights issue was published after approval and registration by the Swedish Financial Supervisory Authority (Finansinspektionen). Västra Hamnen Corporate Finance AB acted as financial advisor during the rights issue and the law firm Vinge as legal advisor.

On July 6, 2021, the successful outcome of the bladder cancer clinical trial was featured in South China Morning Post’s Health & Wellness section. South China Morning Post is Hong Kong-based and has a circulation of 105,000 with 197 million page views per month.

On July 9, 2021, Hamlet Pharma invited investors to take part in on-line meetings to give participants the opportunity to ask questions and discuss the latest developments and future plans for the company.

On July 9, 2021, Hamlet Pharma’s achievements were highlighted during an EU evaluation. Despite the COVID pandemic, the company has fully achieved its milestones. After this successful evaluation, Hamlet Pharma received the second payment from the EIC Accelerator Horizon 2020 fund of approximately 6.7 million SEK.

The EU evaluators state that: "All required milestones and deliverables to date are without any significant deviations. This is particularly impressive considering the global Corona virus pan- demic. To date, the beneficiary has succeeded in manufacturing the Investigational Medicinal Product (IMP) Alpha1H. The company has demonstrated non-clinical improvement of therapeutic efficacy of other cancer drugs like Mitomycin C and Epirubicin, when combined with Alpha1H and successfully continued with the Phase I/II study of Alpha1H in bladder cancer patients. There is evidence of good financial management in this project. The number of financial re- sources utilized to date is proportionate to the achievements of the project to date".

On July 23, 2021, it was announced that Hamlet Pharma’s rights issue was significantly oversubscribed, B units by 260%. The issue guarantees were not used. The rights issue provides the company with approximately 50.4 million SEK, before deductions for issue costs of approximately SEK 4.1 million. Future warranties (TO3 and TO4) will potentially raise an additional SEK 90.7 million SEK before deduction of issue costs of approximately SEK 2.3 million SEK.

On August 27, 2021, the Year-end Report for the fiscal year 2020 – 2021 was published. The focus during the past 12 months has been on i) finishing the evaluation and publication of the first part of the phase I/II trial ii) expanding the clinical trial program to include a dose-escalation part and combination therapy iii) securing the production of Alpha1H for future clinical trials, iv) developing business strategies and identifying partners for Alpha1H and BAMLET and v) securing continued funding of the company.

On September 3, 2021, it was announced that Hamlet Pharma’s conversion of BTU B into shares and warrants of series TO3 B and TO4 B was on September 9, 2021.The first day for trading in warrants of series TO3 B and TO4 B will be September 10, 2021.

Q2

On October 28, 2021, the shareholders of Hamlet Pharma were summoned to the Annual General Meeting on November 25, 2021.

On October 29, 2021, Hamlet Pharma announced that it had secured the production of larger quantities of Alpha1H, using a stable, large scale manufacturing process. Larger amounts of drug will be needed for the continued clinical trial program, which involves larger study populations. Hamlet Pharma is collaborating with Rechon Life Science for the production and formulation of the drug candidate Alpha1H. Rechon is a well-recognized contract manufacturing organization based in Malmö and offers a complete pharmaceutical service including preparation, packaging, and distribution of Clinical Trial Supplies for clinical studies phases I-IV. Production is carried out in accordance with GMP and Rechon is approved for pharmaceutical supply worldwide (including the US).

On November 2, 2021, Hamlet Pharma’s Board of Directors proposed two new members for election to the company’s Board of Directors. Ulla Trägårdh is a lawyer with broad experience in the area of business law. She has been involved in the development of both a major Swedish law firm, as well as a local niche law firm that she established 2003. Lars Hedbys has many years’ experience from the pharmaceutical industry and has founded and listed several life science companies.

On November 4, 2021, the annual report for the fiscal year 2020/2021 was published. It can be found on our website or on Spotlight Stock Market’s webpage.

On November 11, 2021, Q1 for the fiscal year 2021/2022 was published. It can be found on our website or on Spotlight Stock Market’s webpage.

On November 25, 2021, the Annual General Meeting was held. Due to the corona virus pandemic, the meeting was conducted by advance voting with the support of temporary statutory rules. It was decided to appoint Catharina Svanborg, Bengt Westermark, Bill Hansson, Ulla Trägårdh, Lars Hedbys and Helena Lomberg as board members for the period until the end of the next Annual General Meeting. The AGM resolved to approve the income statement and balance sheet as included in the annual report. The AGM resolved to dispose the company’s results in accordance with the Board’s proposal in the annual report. Furthermore, it was decided that no dividend will be paid for the financial year 2020/2021. It was also resolved to grant the members of the Board of Directors and the CEO discharge from liability for the period covered by the annual report presented at the meeting. The relevant members of the Board of Directors or the CEO did not participate in this decision.

On November 30, 2021, the company invited investors to an on-line meeting to summarize the information normally presented at the Annual General Meeting and to provide a forum for a dialogue with the shareholders. About 80 participants took part and the discussions were lively and constructive.

On November 30, 2021, Hamlet Pharma signed a contract with Galenica AB. Hamlet Pharma is proceeding with the development of BAMLET for pharmaceutical use and a necessary first step is to establish technology for large-scale production of BAMLET. A new production method has been developed and patented and will be used as a basis for scaling up the production process together with Galenica AB. The parties have agreed on a development plan, including production technology transfer, testing of biological activity of the product and development of suitable formulations. Galenica AB is a contract research organisation (CRO) providing services in the field of pharmaceutical technology. The company has broad skills and experience in formulation, production and quality control of pharmaceuticals.

On December 7, 2021, Hamlet Pharma announced the new website and recruitment of a new media strategist. Hamlet Pharma increase focus on the company’s digital channels to provide easier access for shareholders and the public. An updated website and digital meetings with shareholders are examples already implemented.

Q3

On January 14, 2022, Strategic recruits to the Hamlet Pharma Think Tank were announced. The company has formed the Think Tank as a forum for strategic discussions important to the company’s future. In addition to the competence that exists in the company, leading experts have been recruited in the areas of drug development, business development, finance, and clinical strategy. The Think Tank will provide a forum for creative discussions and networking, a place where experience and expertise within the company’s major strategic areas will be shared to reach innovative solutions.

On January 17, 2022, the successful completion of the dose-escalation extension of the Phase I/II study was announced. More potent effects of Alpha1H for key study parameters were seen for higher doses. The tumors were more strongly affected by Alpha1H at higher doses than in patients treated with the lower dose, as shown by more extensive shedding of tumor cells and tumor fragments into patient urine. As shown earlier, significant cell shedding or apoptosis did not occur in the placebo group, confirming the treatment effect. The results are very encouraging for our continued work towards Phase III trials.

On January 31, 2022, a newsletter was published to describe data from the dose-escalation study in greater detail. The correlation between dose and effect strongly indicates that Alpha1H has great potential as a drug against bladder cancer.

On February 25, 2022, Hamlet Pharma published the Interim report Q2 for the period October-December 2021.

On March 2. 2022, Hamlet Pharma presented the company on Stockholm Corporate Finance 14th Life Science Capital Market days.

On March 4, 2022, A Successful review of HAMLET Pharma’s EU Horizon 2020 program was announced. Hamlet Pharma has delivered its 18-month report to the European Union’s Horizon 2020 program. The EU reviewer stated that the project has "fully achieved its objectives and milestones for the period" and "remains in line with the objectives". It was mentioned that Hamlet Pharma was one of very few companies that achieved all milestones on time, during the pandemic.

On March 8, 2022 Hamlet Pharma presented at Stockholm Corporate Finance’s 14th Life Science Capital Market days. View Source

Q4

On April 5, 2022, Hamlet Pharma announced that Martin Erixon joins Hamlet Pharma as new CEO. Martin has extensive experience from the Medical/ Pharmaceutical industry as well as from the Food Processing industry. He is a highly motivated team player and negotiator, who strives to find the best solutions in business relationships. In his previous role as advisor to Hamlet Pharma, Martin Erixon has facilitated the discussions with external partners in recent years.

On April 25, 2022, Hamlet Pharma presented at Aktiespararna in Helsingborg.

On May 10, 2022, Hamlet Pharma presented at Naventus Corporate Finance & Partners Healthcare Summit. View Source

On May 13, 2022, Hamlet Pharma presented at the 3rd International Donor Milk Research Congress in Milan. View Source

On May 17, 2022, the subscription price for the exercise of warrants of series TO 3 B was set at 3.28 SEK per share. Upon full exercise of all warrants, the Company will receive an additional maximum of 12.9 MSEK.

On May 18, 2022, Hamlet Pharma published a newsletter highlighting the recent presentations of the company. Hamlet Pharma has participated in a number of recent events, presenting highlights from the promising clinical studies and future strategy. With this newsletter, you are invited to see these presentations by following the links in the text.

On May 20, 2022, Hamlet Pharma published the Interim report Q3 for the period January – March 2022.

On May 27, 2022, Hamlet Pharma published last day for trading in warrants of series TO 3 B is 27th of May.

On June 1, 2022, Hamlet Pharma published an interview with Martin Erixon, the new CEO of Hamlet Pharma. He firmly believes in the company and is full of enthusiasm for a promising future.

On June 2, 2022, Hamlet Pharma published warrants of series TO 3 B were subscribed for approximately 45% and Hamlet Pharma AB (publ) will receive approximately SEK 5.8 million.

On June 13, 2022, Hamlet Pharma published "Brain tumor therapy – A new indication for Hamlet Pharma". A joint development agreement with Neurochase Limited, founded by Professor Steven Gill, a world leading expert in the area of neurosurgery, to develop novel technology and methods to treat Central Nervous System (CNS) tumors with Alpha1H.

Significant events after the fiscal year

On August 2, 2022, Hamlet Pharma published "Full speed ahead! – Hamlet Pharma adapts the clinical trial program for stand-alone use". Hamlet Pharma highlights the development of the clinical protocol in bladder cancer. The company has decided to interrupt the combination study where Alpha1H was used together with a chemotherapy drug. There was no evidence of a therapeutic advantage and the patients experienced side effects, which are not seen with Aloha1H alone. It was also announced that Hamlet Pharma is taking one more step towards the design of the Phase III clinical trial protocol by adding a second treatment round after the completion of the first round of treatment in the ongoing study. These decisions strengthen Hamlet Pharma’s position as a company developing drug candidates with a more beneficial profile than traditional chemotherapeutic drugs.

On August 9, 2022, Hamlet Pharma published "Hamlet Pharma receives a new rapid approval in the Czech Republic". Hamlet pharma announced the rapid approval of Hamlet Pharma’s application to amend the clinical trial of Alpha1H in bladder cancer by the Czech regulatory authorities. This important new part of the ongoing study is now ready to start.

The period in summary

FOURTH QUARTER (APR 1, 2022-JUN 30, 2022)

– Net sales for the quarter totaled KSEK 0 (0)

– Other operating income totaled KSEK 241 (3,310)

– Loss before tax amounted to KSEK -7,851 (-705)

– Loss after tax amounted to KSEK -7,851 (-705)

– Loss per share* was SEK -0.0710 (-0.0070), and SEK -0.0686 after dilution

FULL-YEAR (JUL 1, 2021-JUN 30, 2022)

– Net sales totaled KSEK 0 (0)

– Other operating income totaled KSEK 9,979 (9,340)

– Loss before tax amounted to KSEK -17,197 (-7,722)

– Loss after tax amounted to KSEK -17,197 (-7,722)

– Loss per share* was SEK -0.1556 (-0.0765), and SEK -0.1502 after dilution

– On June 30, 2022, the equity/assets ratio*** was 91.1 (21.6) %

Amounts in parentheses above and below indicate the corresponding value in the preceding year.

* Profit/loss after tax for the period divided by 110,529,666 (100,874,697) and 114,472,907, respectively, where 110,529,666 is the number of shares outstanding on June 30, 2022, and 114,472,907 will be the number of shares if the subscription warrants issued by the Company are exercised. The comparative figure in parentheses was the number of shares on June 30, 2021.

On August 26, 2022 Shanghai Henlius Biotech, Inc. (2696.HK) reported that the NDA for new indication of HANSIZHUANG, serplulimab, an anti-PD-1 mAb independently developed by the company, in combination with chemotherapy for the first-line treatment of patients with locally advanced/recurrent or metastatic esophageal squamous cell carcinoma (ESCC) has been accepted by the National Medical Products Administration (NMPA) (Press release, Shanghai Henlius Biotech, AUG 26, 2022, View Source [SID1234622747]). HANSIZHUANG has been approved by NMPA for the treatment of microsatellite instability-high (MSI-H) solid tumors, and the NDAs of first-line squamous non-small cell lung cancer (sqNSCLC) and first-line extensive-stage small cell lung cancer (ES-SCLC) indications have been accepted. ESCC is the fourth indication for HANSIZHUANG has been accepted by NMPA.

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Professor Jing Huang, the principal investigator of ASTRUM-007 from Cancer Hospital Chinese Academy of Medical Sciences, said, "ASTRUM-007 is a phase 3 clinical study enrolled locally advanced/recurrent or metastatic ESCC patients with PD-L1 CPS≥1 of serplulimab. In the planned interim analysis evaluated by the Independent Data Monitoring Committee (IDMC), the study has met the co-primary endpoints, providing evidence of safety and efficacy. PD-1 inhibitors combined with chemotherapy has become the first-line standard treatment for advanced esophageal cancer in China. We are hoping that the approval of HANSIZHUANG for the treatment of ESCC comes soon and bring a new treatment option to patients living with ESCC. "

Mr. Jason Zhu, President of Henlius, said, "HANSIZHUANG is an innovative mAb independently developed by Henlius, and ESCC is the fourth indication for which the company filed application. Based on the large number of unmet clinical needs as well as the intractable cancers both globally and in China, we developed differentiation strategy around serplulimab to promote the combination immunotherapy of HANSIZHUANG and clinical research, thereby benefiting more patients in China and around the world."

Esophageal cancer is high incidence in China. According to estimates of the prevalence of malignant tumours in China in 2016, there were 253,000 new cases and 194,000 deaths of esophageal cancer, ranking sixth and fifth in malignant tumors in China, respectively[2]. Since the symptoms of early esophageal cancer are often subtle, most patients are diagnosed in the middle or late stages, missing out on surgical treatment. The mainly treatment for advanced patients is systematic treatment (chemotherapy or targeted therapy), but the treatment result is often limited with the highly recurrence and metastasis rate. Therefore, new drugs and treatments are urgently needed. In recent years, immuno-oncology therapy has become one of the research priorities at home and abroad. Many studies have shown that anti-PD-1 mAb combined with chemotherapy can bring survival benefits to patients with esophageal cancer. Immune checkpoint inhibitor combined with chemotherapy has become the first-line standard treatment for esophageal cancer in China[3].

The NDA is mainly based on the results from a randomized, double-blind, multicenter phase 3 clinical study (ASTRUM-007) comparing HANSIZHUANG in combination with chemotherapy (Cisplatin + 5-FU) or placebo in combination with chemotherapy (Cisplatin + 5-FU) as a first-line treatment for patients with locally advanced/recurrent or metastatic esophageal squamous cell carcinoma. In May 2022, the results of interim analysis conducted by IDMC stated that HANSIZHUANG in combination with chemotherapy showed a significant improvement in PFS and OS against placebo in combination with chemotherapy, which met the pre-defined efficacy criteria, with good safety and no detection of new safety signal.

Underpinned by the patient-centric strategy, serplulimab clinical layout covered high incidence tumours

HANSIZHUANG (serplulimab) is the first innovative mAb developed by Henlius. It has been approved by the NMPA for the treatment of microsatellite instability-high (MSI-H) solid tumours. Henlius actively promotes HANSIZHUANG in conjunction with in-house products of the company such as tumour-specific target, angiogenesis target, immunotherapeutic target, etc. and chemotherapy drugs to conduct immune combination therapies. Underpinned by the patient-centric strategy, Henlius has carried out a differentiated and multi-dimensional layout in the field of gastrointestinal cancer and lung cancer, covering a wide variety of indications, such as lung cancer, hepatocellular carcinoma, ESCC, head and neck squamous cell carcinoma and gastric cancer, etc. Up to date, more than 3,100 subjects have been enrolled worldwide for HANSIZHUANG clinical trials.

In the field of gastrointestinal cancer, HANSIZHUANG has been approved for the treatment of MSI-H solid tumours, which could benefit for patients with MSI-H colorectal cancer and MSI-H gastric cancer. In addition, PD-1 inhibitors are less explored in neoadjuvant/adjuvant therapies for gastric cancer, and Henlius has led the way with a Phase 3 clinical study, striving to benefit gastric cancer patients from the early line of immunotherapy. As for the first-line lung cancer treatment, HANSIZHUANG would potentially be the world’s first PD-1 inhibitor for the first-line treatment of SCLC. Furthermore, HANSIZHUANG was recommended by the 2022 CSCO Guidelines for Diagnosis and Treatment of SCLC for the treatment of ES-SCLC and was also granted orphan drug designation by the FDA for treatment of SCLC.

Going forward, Henlius will continue conducting clinical studies for more innovative products, proactively exploring immuno-oncology combination therapy, bispecific antibodies and the antibody-drug conjugates (ADC), committing to bringing affordable and high-quality innovative biologics to patients around the world.

About Serplulimab

HANSIZHUANG (recombinant humanized anti-PD-1 monoclonal antibody injection, generic name: serplulimab injection) is the first innovative monoclonal antibody developed by Henlius. Up to date, 1 indication is approved for marketing in China, 3 NDAs have been accepted by the NMPA, and 11 clinical trials are ongoing across the world.

HANSIZHUANG was approved by the NMPA for the treatment of MSI-H solid tumors in March 2022 and actively promotes its synergy with in-house products of the company and innovative therapies. It has successively obtained clinical trial licenses in China, the United States, the European Union and other countries and regions to initiate 11 clinical trials on immuno-oncology combination therapies worldwide in a wide variety of indications, such as lung cancer, esophageal carcinoma, head and neck squamous cell carcinoma and gastric cancer, etc., and covering the full range of first-line treatments of lung cancers. As of now, the company has enrolled more than 3,100 subjects in China, Turkey, Poland, Georgia and other countries and regions, and the proportion of Caucasian is over 30% in two MRCTs, making HANSIZHUANG an anti-PD-1 mAb with one of the largest global clinical data pools. The NDAs of the first-line treatment for squamous non-small cell lung cancer (sqNSCLC), extensive small-cell lung cancer (ES-SCLC), and esophageal squamous cell carcinoma (ESCC) have been accepted by the NMPA, which makes HANSIZHUANG potentially the world’s first anti-PD-1 mAb for the first-line treatment of SCLC. Furthermore, HANSIZHUANG was recommended by the 2022 CSCO Guidelines for Diagnosis and Treatment of Small Cell Lung Cancer (SCLC) for the treatment of ES-SCLC and was also granted orphan drug designation by the FDA for treatment of SCLC.