Pipeline

Kamada has been able to leverage its expertise gained from the production of Glassia to develop a stable, high purity Inhaled AAT for AATD, an inhaled AAT product candidate for the treatment of AATD.

Existing treatment for AATD require weekly intravenous infusions of AAT therapeutics. We believe that Inhaled AAT for AATD will significantly improve the patient’s disease condition and the quality of life of the patients versus current invasive weekly treatment that requires uncomfortable infusion, consumption of time and administration by a medical professional. If approved, Inhaled AAT for AATD is estimated to be the first AAT product that is not required to be delivered intravenously but, instead is administered by a user-friendly, lightweight and silent nebulizer in up to two short daily sessions.

We estimate that Inhaled AAT for AATD will increase patient convenience and reduce or replace the need for patients to use intravenous infusions of AAT products, decreasing the need for clinic visits or nurse home visits and reducing medical costs.

Inhaled AAT for AATD has been designated as an orphan drug for the treatment of AATD in the United States and Europe.

GvHD is a common complication following allogeneic tissue transplantation. It is typically associated with stem cell transplantation, but the term also applies to other forms of tissue grafts. In GvHD, immune cells (white blood cells) in the tissue (the graft) recognize the recipient (the host) as “foreign,” and then attack the host’s body cells.

GvHD occurs in 30% to 70% of patients who undergo allogeneic hematopoietic stem cell transplantation (HSCT), i.e. transfer of cells from a healthy allogeneic (non-self) bone marrow donor, usually as a treatment for leukemia or other blood cancers or blood conditions. One of the most common and dangerous complications of HSCT is GvHD. GvHD is expressed in damage to the recipients’ tissues, most prominently liver, gastrointestinal system, skin and mucosal tissues, and is a major cause of morbidity and mortality in these patients.

Intravenous glucocorticoids such as prednisone are the standard of care in the treatment of acute GvHD and chronic GvHD. The use of these glucocorticoids is directed to suppressing the T cell-mediated immune onslaught on the host tissues; however, in high doses this immune suppression raises the risk of infections and leukemia relapse.  More than 50% of patients do not respond well to steroids, and consequently have very low survival rates.

Preliminary human and animal studies indicate that AAT may be able to treat and reduce the severity of GvHD. It is well known that plasma-derived AAT has been used since the 1980’s and its safety profile is very high.

In recent years, AAT has been investigated extensively and found to have anti-inflammatory, tissue-protective, immune-modulatory and anti-apoptotic properties in direct or indirect consequence of its underlying anti-protease capabilities. These properties may attenuate inflammation by lowering levels of pro-inflammatory mediators such as cytokines, chemokines and proteases that are associated with this severe disease.

In January 2018, Kamada announced a collaboration with the Mount Sinai Acute GvHD International Consortium (MAGIC) for the conduct of a clinical trial assessing the safety and preliminary efficacy of our AAT product as preemptive therapy for patients at high-risk for the development of steroid-refractory acute GvHD (SR-aGvHD). The study will be conducted in five U.S. centers, all of which are members of MAGIC, which consists of 23 Bone Marrow Transplantation (BMT) centers in the United States, Europe and Asia, and conducts clinical trials to prevent and treat GvHD following BMT. This is an investigator-initiated study, co-funded by Mount Sinai and our company, and is sponsored by the Icahn School of Medicine at Mount Sinai (ISMMS).

Kamada also collaborates with myTommorows, a company which provides services to patients and physicians in need of diagnostic tests and drugs in development, to provide early access throughout Europe to Kamada’s proprietary, highly-purified, liquid form of Alpha-1 Antitrypsin (AAT) to treat bone marrow transplant patients who develop steroid refractory Graft-Versus-Host Disease (GvHD).

Through myTomorrows’ web-based platform, Kamada’s AAT is now available to physicians and patients in Europe via Early Access Programs. These programs provide physicians and patients facing unmet medical needs with access to development stage drugs in instances that meet regulatory requirements.

Lung transplantation is the last resort for patients who suffer from an end stage lung disease. While survival rates are improving, there is a constant need for reducing acute and chronic rejection rates.

Long term graft and patient survival are limited by both acute and chronic allograft rejection, with a median survival of just over six years.1 Fully one-third of all lung transplant recipients experience acute rejection in the first year and 40% will develop chronic rejection within the first five years.

AAT has been investigated extensively in recent years and has been found to have anti- inflammatory,tissue-protective, immune-modulatory and anti-apoptotic properties in direct consequence of its underlying anti-protease capabilities. These properties may attenuate inflammation by lowering levels of pro-inflammatory mediators such as cytokines and proteases that are associated with organ transplantation rejection, such as lung transplantation.

Kamada collaborates with Baxalta to Initiate a Phase 2 clinical trial with intravenous Alpha-1 Antitrypsin for the prevention of lung transplant rejection

The Phase 2 trial is a randomized, open-label, single-site study of 30 lung transplant recipients to evaluate the safety and efficacy of IV AAT on top of standard-of-care (SOC) versus SOC. The study is randomized 2:1 with 20 patients in the treatment group receiving IV AAT treatment every other day for 14 days, then once every two weeks until week eight, followed thereafter by monthly treatments. The 10 patients in the control group will be treated with SOC, which includes systemic corticosteroids and immunosuppressants. Following one year of AAT treatment, there will be a one-year follow-up.

Current treatment options, such as immunosuppressants, have limited efficacy and can have significant adverse side effects and co-morbidities. Preclinical data published in Blood suggest that IV AAT has an immunomodulatory and anti-inflammatory mechanism of action that would support its role in the prevention of lung transplant rejection.

The study is being conducted at Rabin Medical Center – Beilinson Hospital in Israel and is being led by principal investigator, Prof. Kramer.

Kamada reported interim results which summarize data from the first six months of treatment for the initial 16 patients in the study.

Type 1 Diabetes is an autoimmune disease in which the pancreatic beta cells responsible for secretion of insulin are attacked and destroyed by the immune system. According to estimates by the U.S. Centers for Disease Control, more than 10 million people throughout the world suffer from Type-1 Diabetes with 100,000 new patients diagnosed annually. According to estimates by the American Association for Type-1 Diabetes, approximately three million people in the United States suffer from Type-1 Diabetes, with 30,000 new patients diagnosed annually.

Studies have demonstrated that even though the level of AAT protein in Type-1 Diabetes patients may be normal, the activity of the AAT protein in these patients is significantly lower than in healthy people. Because AAT has proven anti-inflammatory responses, treatment by AAT protein in the initial stages after diagnosis of Type-1 Diabetes may prevent or may delay the inflammation that is caused by the autoimmune destruction of the pancreatic cells. As a result, AAT therapeutics may slow the progression of the development of newly diagnosed Type-1 Diabetes and improve prognosis.

Kamada reported topline results of a phase II clinical trial in pediatric and young adult patients suffering from Type-1 Diabetes (T1D). This double-blind, placebo-controlled, multi-center clinical trial was designed to evaluate the efficacy and safety of AAT IV in halting disease progression in pediatric and young adult patients newly diagnosed with T1D. Study endpoints included beta cell function assessment as measured by change in C-peptide parameters, glycemic control represented by HbA1C levels and insulin daily dose.

Kamada’s AAT IV demonstrated a very good safety profile in T1D pediatric and young adult patients treated in the Phase 2 study, similar to that observed with GLASSIA® for the treatment of Alpha-1 Antitrypsin Deficiency.

Analysis of the study data for the 12-18-year-old patient subgroup treated, shows that AAT may have a beneficial effect on beta-cell function, HbA1c level and insulin daily dose intake. This effect may potentially reduce future severe disease complications.