Nyheter | Spotlight
Hem

Reports

Publicerat: 2019-11-08 08:30:00

Hamlet Pharma AB: Interim Report 1   2019-07-01 - 2019-09-30

Opening remarks

The first quarter of the fiscal year 2019/2020 has been one of the most exiting in the history of Hamlet Pharma AB. As previously announced, the result from the first double blind, placebo controlled clinical study was announced at the end of July. It was with great pleasure and enthusiasm we concluded that Alpha1H treatment is effective in patients with bladder cancer without causing severe side effects. 

Alongside the clinical trial, the Company has laid the foundation for continued clinical development. In an animal model of bladder cancer, research has shown that a higher dose of Alpha1H increases the therapeutic effect. As previously announced, we have received regulatory approval for a dose-escalation study in patients with bladder cancer, with the aim of identifying an optimal dose for future studies. Moreover, we have gained support to continue the clinical trials in Prague with the excellent clinical team and external partners.

We are extremely grateful for the professionalism shown by our employees and external partners, which is a prerequisite for achieving the clinical and scientific goals set up by the company. We would like to take the opportunity to thank our investors and shareholders for their confidence in us, and we are looking forward to the next step in the development of Alpha1H towards an approved drug for the treatment of cancer.

Catharina Svanborg                                        Mats Persson

Chairperson of the Board & CMO                  CEO

Significant events during the first quarter

On July 18, 2019, the Company announced the positive outcome of the bladder cancer trial. The objective of the phase I/II trial was to investigate the safety and efficacy of Alpha1H treatment in patients with bladder cancer. Consistent with the results from animal toxicity studies, no side effects due to Alpha1H were registered, indicating that the treatment is safe and well tolerated. Alpha1H also demonstrated a very clear and significant effect compared to the placebo group. Furthermore, some patients treated with Alpha1H secreted whole tumour fragments, indicating efficacy of Alpha1H compared with placebo. Alpha1H also induced cell death in the tumour through apoptosis, which is a process by which tissues remove dead cells wihout damage to the tissue. These findings support the mechanisms of action for Alpha1H demonstrated in the laboratory experiments and in animal studies.


Dose-escalation studies in an animal model of bladder cancer

To counteract the aggressive behavior of cancer cells, therapies are often highly toxic and almost invariably accompanied by severe side effects. This study in an animal model addressed if a better balance between efficacy and toxicity can be attained, using the tumoricidal peptide-oleic acid complex Alpha1H. Results in an animal model show that a dose-dependent increase in therapeutic efficacy can be achieved, without a parallel increase in side effects. Intravesical instillation of Alpha1H resulted in a dose-dependent reduction in tumor size, bladder size, bladder weight and the tumor markers Ki-67, Cyclin D1 and VEGF. In parallel, the expression of cancer-related genes was inhibited. Remarkably, toxicity for healthy tissue was not detected in treated tumor-bearing mice even at the highest concentration of Alpha1H as organ weights, clinical chemistry and hematology parameters remained unaffected. The results define a dose-dependent therapeutic effect of Alpha1H in a murine bladder cancer model, without local or systemic side effects. 

Figure, please see attached pdf


Significant events after the first quarter

On October 7, 2019, the Company received KSEK 12,950 by redemption of the first serie of subscription warrants. No issue costs were paid. For more information, please see below under the heading ‘Issue of new shares and subscription warrants’.

On October 11, 2019, the Company released further data from the clinical study. Detailed data analyses and statistical tests were performed.


Safety Analyses

The objectives of the ongoing clinical trial are to assess the safety and efficacy of Alpha1H treatment in patients with bladder cancer. There were no side effects related to the Alpha1H treatment showing that instillations of 1.7 mM of Alpha1H into the bladder can be regarded as safe.


Efficacy Analyses

Several efficacy end points were met.

I. Alpha1H triggered massive shedding of tumor cells into patient urine

A rapid increase in cell shedding was detected in patients, who received Alpha1H compared to placebo (P<?0.0001). Cell shedding occurred each time the patients received Alpha1H (Visit 1-6). A similar increase was observed for tumor fragments, which were released into the urine of patients receiving Alpha1H (P<?0.0001).

II. Alpha1H triggers cell death in the tumor (apoptosis)

To examine how the tumor responds to Alpha1H treatment, biopsies were obtained from the tumor at the time of surgery. Cell death was defined by TUNEL staining, which detects apoptosis; a beneficial, non-toxic form of cell death. A highly significant increase was observed, compared to the placebo group. The results suggest that Alpha1H accelerates cell death in the tumor.

III. Alpha1H is taken up by tumor cells

By fluorescence microscopy, we showed that Alpha1H was taken up by tumor cells, providing evidence that the drug candidate alpha1H interacts with the tumor.  


Follow up studies

The ongoing clinical study includes an extended follow-up period of 24 months for each participating patient. 

The dose escalation study amendment was recently approved by the Czech authorities,. Two dose levels of Alpha1H, 8 mM and 17 mM, will be tested. Up to 12 additional subjects may be included depending on the safety outcome. A Maximum Tolerated Dose (MTD) will be defined. 


Figures

FIRST QUARTER (JUL 1, 2019-SEP 30, 2019)

– Revenue for the first quarter totaled KSEK 0 (0)

– Profit/Loss before tax amounted to KSEK -2,743 (-2,980)

– Profit/Loss after tax amounted to KSEK -2,743 (-2,980)

– Profit/Loss per share* was SEK -0.0868 (-0.0973), and SEK -0.0816 after dilution

– At September 30, 2019, the equity/assets ratio** was 87.0% (87.7%)

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

* Profit/loss after tax for the period divided by 31,624,899 (30,624,899) and 33,624,899 shares, respectively, where 31,624,899 is the number of shares outstanding at September 30, 2019, and 33,624,899 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 at September 30, 2018.

** Equity divided by total capital.

Hamlet Pharma AB

Hamlet Pharma, whose shares are traded on Spotlight Stock Market, is part of a Group and is a subsidiary company of Linnane Pharma AB, which owns about 53% of Hamlet Pharma AB. The Company is engaged in drug development based on a tumouricidal protein-lipid complex, HAMLET, formed by two generally regarded as safe (GRAS) molecules present in human milk. The novel therapeutic entity HAMLET is formed when alpha-lactalbumin (the primary protein component of human milk) undergoes a conformational change and binds to oleic acid. The aim is to develop drugs that can primarily be used for the treatment and prevention of cancers. HAMLET selects and removes tumour cells efficiently and has not shown toxicity in two proof-of-concept studies in humans. The agent has shown a therapeutic effect on skin papillomas in a placebo-controlled clinical trial and induces shedding of dead cancer cells after injection into the bladder of patients with bladder cancer.

Alpha1H is the synthetic variant of HAMLET, which has enabled development of the agent for clinical trials. Alpha1H kills different types of tumour cells and has demonstrated therapeutic effects on bladder cancer in animal models. Hamlet Pharma has one ongoing Phase I/II clinical trial with Alpha1H in patients with bladder cancer, a costly form of cancer that is difficult to treat, and intends to expand its activities into other types of cancer. The first results from the ongoing clinical PhaseI/II study shows no side effects of Alpha1H, indicating that the treatment is safe and well tolerated. Alpha1H also demonstrated clinical efficacy compared with patients who received placebo.

The company’s operations are based on R&D. The Company has therefore concluded an agreement with Lund University to ensure that Hamlet Pharma gains access to the research findings underlying the continued development of its research portfolio. The protein-lipid complex HAMLET is formed when alpha-lactalbumin (a human milk protein) binds to oleic acid (a fatty acid), which is also present in milk. The Company has also identified the active components of the HAMLET molecule that are responsible for the tumoricidal activity, and developed large-scale production of these components. The peptide complex that we have named Alpha1H has demonstrated efficacy on bladder cancer in relevant animal models and is currently being tested in a clinical trial. Alpha1H has been granted patents in both Europe and the US.


Revenue and earnings

During the first quarter, Hamlet Pharma’s sales amounted to KSEK 0 (0). Costs were related to the continued R&D activities of the research team at Lund University as well as costs for the ongoing clinical trial in bladder cancer patients. The team at Lund University is responsible for the development of manufacturing methods, stability testing and chemical and functional characterization of existing and new drug substances, and plays a key role in the coordination of laboratory testing in the clinical trial. Costs were also related to production of the Alpha1H peptide and preparation of the clinical trial materials for use in ongoing and forthcoming clinical trials. Loss before tax for the first quarter was KSEK -2,743 (-2,980). 


Financial position

No financial activities have affected the Company during the first quarter. However, the Company have issued subscription warrants after the end of the quarter. 

At the end of the first quarter, the equity/assets ratio was 87.0% (87,7%), and the Company’s cash and cash equivalents were KSEK 5,041 (12,366). The Company expects that the issuances in October 2019 and January/ February 2020 will generate approximately MSEK 26, which will secure continuing operations during the fiscal year.

Read more under New share issue and subscription warrants.

Cash flow and investments

No intangible assets were capitalized during the period, since the Company is in an R&D stage. R&D costs are therefore recognized as operating expenses in the income statement. No new investments in tangible assets were capitalized during the first quarter.


The share

At September 30, 2019, the number of shares totaled 31,624,899. The Company’s shares have been traded on Spotlight Stock Market (formerly AktieTorget) since October 23, 2015. Spotlight Stock Market is the secondary name of ATS Finans AB, a securities company under the Swedish Financial Supervisory Authority’s supervision.


Issue of new shares and subscription warrants

On February 1, 2019, the Board of Hamlet Pharma AB decided to implement a private placement of shares with subscription warrants that would generate proceeds of approximately MSEK 36 for the Company if fully exercised. 

The Company’s share capital was increased by SEK 30,000 by issuing 1,000,000 shares. The Board’s decision also means that a maximum of 2,000,000 subscription warrants will be issued, entitling the holders to subscribe for a maximum of 2,000,000 shares. If the subscription warrants are exercised, the Company’s share capital will increase by a further maximum of SEK 60,000. The new shares will not carry the right to a dividend until the first record date after the shares have been registered with Euroclear Sweden AB.

In February 2019, the Company implemented the adopted new issue totalling KSEK 10,350, with issuance costs of a modest KSEK 12, generating KSEK 10,338 net. In October 2019, the Company received KSEK 12,950 from redemption of the first serie of subscription warrants. No issue costs were paid, making the entire sum available to the company. A second series of subscription warrants scheduled for January/February, can potentially generate an additional KSEK 12,950.


Basis of preparation for the interim report

The Company prepares its accounts in accordance with the

Swedish Annual Accounts Act and the K3 framework (BFNAR

2012:1) of the Swedish Accounting Standards Board.

Review

This interim report has not been audited.

Financial calendar

Annual General Meeting for

the 2018/19 fiscal year                                        November 21, 2019

Interim report for Q2, 2019/20                             February 28, 2020

Interim report for Q3, 2019/20                             May 22, 2020


For Income statement, Balance sheet, Cash flow statement and Equity, please see attached pdf cop.

For more information, please contact

Catharina Svanborg, Chairperson of the board, Hamlet Pharma, +46 709 42 65 49

catharina.svanborg@med.lu.se

Mats Persson, CEO Hamlet Pharma, +46 705 17 67 57

mats.persson@hamletpharma.com 

About HAMLET Pharma

HAMLET Pharma, listed on Spotlight, develops drugs based on the unique tumoricidal protein-lipid complex, HAMLET, formed by two natural and harmless molecules found in breast milk. Development focuses primarily on drugs, for the treatment and prevention of cancer. HAMLET kills tumour cells and has proven safe in proof-of-concept studies in animal models. HAMLET has also shown therapeutic efficacy on skin papillomas in a placebo-controlled clinical trial and caused shedding of dead cancer cells, after injection into the bladders of patients with bladder cancer. A phase I/II clinical trial is ongoing in patients with bladder cancer, using the synthetic peptide-based compound Alpha1H. The first results from the ongoing clinical PhaseI/II study shows no side effects of Alpha1H, indicating that the treatment is safe and well tolerated. Alpha1H also demonstrated clinical efficacy compared with patients who received placebo.

HAMLET is a registered trademark of HAMLET Pharma.

Läs mer hos Cision
Läs mer om Hamlet Pharma AB