Our most advanced product in development is our patented Topical Interferon Alpha-2b. We are developing this product in cooperation with US-based Schering-Plough Corporation as a treatment for lesions affecting the ano-genital tissues caused by human papilloma virus (HPV) infections.

Topical Interferon Alpha-2b incorporates Helix’s proprietary Biphasix™ drug delivery technology. It is a topical preparation that is intended to be easily self-applied to HPV-infected tissues, in order to deliver interferon alpha-2b into the skin and mucosal tissues.

Interferon-alpha therapy is often prescribed to patients by way of injection to augment their innate defense system capabilities by complementing the effect of interferon alpha-2b naturally produced by the body. Injectable preparations of the interferon alpha-2b drug compound have been on the market in North America and Europe since the mid 1980s, demonstrating a history of proven effectiveness against viral infection, including HPV.

Helix’s Topical Interferon Alpha-2b is intended to offer a superior means of delivering interferon-alpha therapeutically into diseased skin or mucosal tissues by leveraging the capabilities of the Biphasix™ drug delivery technology and eliminating the need to inject interferon-alpha by syringe.

Interferon alpha-2b is believed to function in an immunomodulatory fashion to promote an innate immune system response to viral pathogens by acting upon external cellular receptors and stimulating a host of intracellular and extracellular activities. Within the infected cell, interferon alpha-2b action is thought to stimulate the induction of enzymes such as 2'5' oligoadenylate synthetase and protein kinase R (PKR), which function to cause degradation of viral RNA and inhibit protein synthesis to antagonize viral propagation. Extracellularly, interferon alpha-2b is thought to also enhance the expression of human leukocyte antigens (HLAs) and other HPV-specific antigens on the cell surface, thereby promoting recognition of the infected cells by cytotoxic T cells, natural killer cells and other cells of the innate immune response.

Helix’s Topical Interferon Alpha-2b is intended to facilitate the transport of interferon alpha-2b across the surface of the skin/mucosa in order to permit access to the cells of the underlying basal epidermal layers where viral infection predominates. The exact mechanism by which Helix’s Biphasix™ technology accomplishes this is not fully characterized. However, it is theorized that the cream matrix, upon application to the skin/mucosal surface, temporarily improves the emolliency and fluidity of the skin, which is thought to permit free drug diffusion to the underlying viable epidermis. The viable epidermis is the location wherein HPV infection is known to induce hyperplasia of the intermediate viable epithelial layers. Improved fluidity of the stratum corneum in response to Topical Interferon Alpha-2b application is thought to be achieved by virtue of the constituency of the cream, which includes a combination of common emollients and surfactants, in addition to agents necessary to preserve the integrity of the cream and its drug payload.

Human Papilloma Virus (HPV) infections have reached epidemic proportions in the world, with over 40 million people estimated to be infected with the virus in North America and Europe combined^1,2. According to the American Social Health Association, the virus is the most common sexually transmitted disease known today, primarily affecting sexually active youth between the ages of 15 and 25, and it continues to spread at a rate of over 6 million new cases per year in the US alone.

HPV infection is known to cause hyperplasia of the intermediate viable epithelial layers of the skin. Unless resolved by the effects of the natural host immune system or otherwise by medical intervention, this rapid and unmediated cellular proliferation may proceed to cause any one of a range of cancerous conditions of the ano-genital tissues. Among these disease states, we are developing Topical Interferon Alpha-2b as a treatment for two of the most common manifestations of HPV infection; (i) cervical dysplasia, which is a potentially pre-cancerous condition of the female cervix and (ii) ano-genital warts, a generally benign lesion-bearing condition of the external ano-genital tissues.

<sup>1. Wallin K.L. et al. New England Journal of Medicine. 1999;341:22:1633-88
2. Tyring S.K. The American Journal of Medicine. 1997;102:5A:1-43</sup>

Infection with HPV is now regarded as the definitive cause of cervical cancer in women. Once infected, women may experience progressively deteriorating disease states of the cervix unless the viral action is successfully combated by the human immune system or today's interventional medical treatments. In the United States, for instance, there are almost 2 million women diagnosed each year with potentially precancerous squamous intraepithelial lesions of the cervix³, for which there is no pharmaceutical treatment available today.

At present, treatment is limited to invasive destructive procedures such as surgery and laser therapy, which, due to associated pain and potentially serious side effects, are not usually prescribed unless the cervical disease is determined to be in the more advanced dysplastic stages.

Helix is developing its Topical Interferon Alpha-2b as a potential new, non-invasive means of treating these pre-cancerous cervical disease states with a view to providing a therapy that has no painful or damaging side-effects to the cervical tissues. The Company is hopeful that this may ultimately allow physicians to prescribe treatment early on in the development of the disease to prevent progression to cervical cancer and eliminate the need for destructive medical intervention.

^{3. Schiffman M. et al. Archives of Pathology and Medicine. 2003;127:8:946-949} 

Another disease state induced by ano-genital HPV infection is a condition referred to as condylomata accuminata, or ano-genital warts. Ano-genital warts result from HPV infection of the external genitalia, and can manifest as outwardly visible growths of varying sizes and shapes in both men and women. Helix is developing Topical Interferon Alpha-2b for liberal application to the genitalia of patients with ano-genital warts as a means of delivering potent Interferon-alpha therapy intradermally across the entire surface of the external genitalia to combat the underlying viral infection.

The US Center for Disease Control (CDC) estimates that upwards of 750,000 people develop ano-genital warts each year in the US alone. However, in contrast to women in the Western world who are subject to routine gynecological examination, many HPV-infected men may go undiagnosed without proper medical assessment. Accordingly, in addition to the reported number of diagnosed cases of ano-genital warts each year, it is believed that there are a substantial number of infected men who have not sought medical assessment.

Existing therapies for cervical and external ano-genital human papilloma virus (HPV) infection are limited and, due to irritating, painful and destructive properties, they all share a common drawback: existing therapies only target visibly apparent HPV-induced lesions (e.g., visibly apparent ano-genital warts). This practice has limitations from a therapeutic perspective, because HPV infection is often characterized by sub-clinical viral presence that is not clinically palpable.

Helix’s Topical Interferon Alpha-2b, by comparison to today's therapies, is intended for liberal application to the surface of the skin or mucosa, due to its anticipated relatively non-irritating properties. Consequently, Helix’s Topical Interferon Alpha-2b is believed to achieve drug delivery across a broad tissue surface area in order to target the HPV infection widely and efficiently. Because of its anticipated effectiveness against both visibly-apparent and sub-clinical HPV infection, we expect Topical Interferon Alpha-2b to have significant and marketable advantages over today's available treatments.

Helix is not aware of any other interferon alpha-2b cream product under development today. Helix believes that its Biphasix^TM formulation is specialized and unique among today’s dermal delivery vehicles in being able to offer a stable cream dosage form capable of delivering interferon alpha-2b into the skin and mucosal tissues.

The launch of HPV vaccines was an important step in the fight against HPV infections. Helix believes that the vaccines are complementary to Topical Interferon Alpha-2b. Companies such as Merck and Co. (“Merck”) and GlaxoSmithKline Inc. (“Glaxo”) have developed vaccines that are designed to protect against infection from several specific subtypes of HPV.

While such vaccines have the potential to be significant medical advancements, they are designed primarily to offer a means hopefully to prevent adolescent youths from becoming infected in the first place, rather than to treat patients once infection has occurred. As such they are intended to be essentially prophylactic in nature rather than therapeutic, Topical Interferon Alpha-2b is expected to offer a broadly applicable and efficacious therapeutic option to persons already infected or that contract virtually any of the wide variety of HPV subtypes linked to the development of cervical cancer and ano-genital warts.

Helix has entered into an agreement with Schering-Plough which grants Schering-Plough the option to obtain an exclusive worldwide license to use Helix’s Biphasix™ technology in pharmaceutical products containing interferon alpha-2b. Schering-Plough's option may be exercised at any time up to a specific period following the successful completion of Phase III clinical trials. Included in the option agreement are terms for the grant of a license to Schering-Plough that provides for milestone payments and royalties on product sales.

Helix’s focus together with Schering-Plough, is to develop Topical Interferon Alpha-2b initially for the indications of cervical dysplasia and ano-genital warts. Schering-Plough Corporation is a world leader in the production and sale of interferon alpha-2b therapeutics.

Helix commenced the clinical investigation of its Topical Interferon Alpha-2b for two possible therapeutic indications:

- Low-grade cervical lesions
- Ano-genital warts

The Company has completed a Phase II clinical study for the first potential indication above, and has completed enrollment for the ano-genital warts Phase II trial.  Data from the second trial is expected during the second half of calendar 2010.  Finally, a Phase II pharmacokinetic trial is ongoing to confirm that interferon alpha-2b does not reach the systemic circulation. 

Helix has announced positive results from a phase II clinical study of its Topical Interferon Alpha-2b in women with human papilloma virus (HPV) induced low-grade cervical lesions. The study showed a clinically efficacious response to treatment in nearly half of the treated patients. In addition, the product demonstrated an excellent safety profile, with no significant local intolerance or drug-related serious adverse event observations.

A total of 41 women with cytologically confirmed, HPV-induced low-grade squamous intraepithelial lesions (LSIL) of the cervix were studied across four sites in Germany, under the direction of Prof. Dr. med. Achim Schneider M.P.H., a world expert in the field of cervical cancer and Director of the Department of Gynaecology at the Charité University Hospital in Berlin.

LSIL represents the mild-to-moderate forms of cervical dysplasia which may progress to cervical cancer in women. In the United States alone, an estimated 1.4 million women annually are diagnosed with LSIL. At present, there is no pharmaceutical therapy available to these patients.

Twenty women received Topical Interferon Alpha-2b, self-administered intravaginally three times per week for a period of 6 weeks with a follow-up evaluation at 12 weeks, compared with 21 separately studied women who received no treatment whatsoever over the same study period.

The primary endpoint and main outcome for both groups was the Pap-response rate defined as the proportion of patients with resolution of their abnormal Pap smear LSIL cytology to normal during the 12 week study duration. Pap smear normalization was considered to occur if the patient's Pap smear improved to group II or better from any of Pap smear groups IIW through IIID as per the common European standard, "Munich Classification System" of LSIL cytology. Pap smear testing is a leading method to diagnose potentially precancerous cervical disease caused by HPV in women today.

Nearly half (46.7%) of the women in the treated per-protocol population had their abnormal Pap smears revert to normal during the 12 week period, compared with only 15.8% of the untreated women (i.e., nearly a three-fold improvement). Of these women, one treated patient's LSIL cytology returned following the end of treatment, which suggests that a longer dosing regimen may be advisable in future studies.

Furthermore, upon stratification of the patients according to the North American definition of LSIL cytology (i.e., "The Bethesda Classification System"), the relative difference in the Pap-response rate between the treated and untreated patient groups increased substantially. Using this approach, only those women who entered the study belonging to the Pap smear group IIID classification (i.e., the more advanced/serious Pap smear diagnosis described above) were evaluated. Of the women in the stratified per-protocol treatment population, 42.9% experienced normalization of their Pap IIID smear, whereas none (0.0%) of the untreated Pap IIID women experienced improvement.

Beyond the Pap-response rate efficacy parameter, all other efficacy parameters evaluated showed the same tendency in favour of treatment. For example, 60% of the treated women experienced resolution of their associated abnormal cervical findings upon colposcopic diagnosis versus only 9.5% of the untreated women.

Helix is committed to further advancing its clinical development program for this extremely prevalent condition, with a view to bringing this product to market as expeditiously as possible.

Based on the positive findings from its German phase II program, Helix plans to progress to large, randomized, placebo-controlled double-blind studies to evaluate the product in an expanded patient population. Helix believes that study protocol improvements may allow the clinical outcomes to be enhanced even further. Preparations are underway in anticipation of IND and CTA filings in the U.S. and Europe respectively before the end of the 2009 fiscal year.

Helix has completed a second Phase II trial of Topical Interferon Alpha-2b for the treatment of ano-genital warts (condylomata accuminata) associated with HPV infection. The trial, which took place in Sweden and Germany, was designed to assess the efficacy and safety of Topical Interferon Alpha-2b compared with placebo using a double-blind, randomized design over an examination period of four months per patient. One hundred twenty patients were enrolled in the trial. Half received a placebo and half received Topical Interferon Alpha-2b. Only female subjects were enrolled in the trial to avoid inter-sex treatment variations at this stage.

The trials showed no statistically significant treatment effects between the treatment and the placebo groups. Topical Interferon Alpha-2b was very well tolerated with no serious adverse affects related to the treatment and any local skin reactions were mostly absent or mild in both groups, indicating the safety of Topical Interferon Alpha-2b. The Company will be considering the results of the AGW study in detail to determine its next steps forward for this indication, if applicable.


Topical Interferon Alpha-2b is a drug product candidate under investigation by Helix BioPharma Corp. Descriptions of the mechanism by which Topical Interferon Alpha-2b and the core Biphasix™ technology functions or will function are speculative and are based on scientific theories advanced by the Corporation. The Corporation is actively engaged in ongoing investigative research with Topical Interferon Alpha-2b , through which it will attempt to test its theories. The Corporation offers no guarantee that its theories will be proven, nor that Topical Interferon Alpha-2b will ultimately yield a medicinal therapeutic.