- 4/12 patients (33%) showed evi­dence of stable disease; 2 patients for more than 130 days
- A clin­i­cally-relevant mean time to next ther­apy of 51 days
- PAT-SM6 specifically targets myeloma tumour cells in vivo and stimulates signifcant immune responses
- All dose levels admin­istered were safe with no adverse events observed
- No evi­dence of immunogenicity; PK analysis showed PAT-SM6 to have a half-life of 7 hrs

Melbourne, Australia (Press Release) - Patrys Limited (ASX: PAB; “the Company”), a clin­i­cal stage bio­tech­nology com­pany, is pleased to announce the final results from its Phase I/IIa, open-label study in patients with refractory or re­lapsed multiple myeloma (MM).

This trial was conducted in 12 patients (10 male and 2 female, median age 71 years) with refractory or re­lapsed MM. On average each patient had received five prior lines of ther­apy, in­­clud­ing proteasome inhibitors, immuno­modu­la­tory (IMID) drugs or stem cell trans­plan­ta­tion.

Twelve patients (3 in each cohort) received 4 in­tra­venous infusions of PAT-SM6 at 0.3mg/kg, 1mg/kg, 3mg/kg or 6mg/kg per dose. All patients were then assessed for a response at 36 days post final treatment.

The pri­mary end­point of the study was safety and tolerability. At all dose levels tested, PAT-SM6 was well tol­er­ated with no serious adverse events (SAEs) or dose limiting toxicities being reported. A maximal tol­er­ated dose (MTD) was not reached.

Secondary end­points were designed to measure efficacy as determined by a series of well-established laboratory assays. Overall, 4/12 patients (33%) treated with PAT-SM6 showed evi­dence of stable disease (SD) according to the Inter­na­tional Myeloma Work­ing Group (IMWG) criteria. One patient who received 3mg/kg of PAT-SM6 was stable for 138 days before addi­tional ther­apy was needed whilst another patient, who received 6mg/kg of PAT-SM6, has been stable for 154 days and is cur­rently ther­apy free.

These data compare favorably with another anti­body (Elotuzumab) cur­rently in Phase 3 com­bi­na­tion trials for MM. When tested in a Phase I trial, 26.5% (9/35) patients treated with in­creas­ing doses of Elotuzumab (0.5– 20mg/kg) responded with SD. Like PAT-SM6, this anti­body was used as a single agent. The in­­for­ma­tion on the clin­i­cal efficacy of Elotuzumab is publicly avail­able.

Importantly, patients treated with PAT-SM6 had a mean time to next ther­apy of 51 days which is considered clin­i­cally sig­nif­i­cant.

Patients who had received prior treat­ment with pro­te­a­some inhibitors responded much better to PAT-SM6 treat­ment than patients who had been pre­vi­ously treated with IMIDs or other chemotherapeutics. This ob­ser­va­tion is very exciting as it indicates that PAT-SM6 may act synergistically with pro­te­a­some inhibitors (such as Carfilzomib) to induce better clin­i­cal responses. Such a hypothesis will be tested in Patrys’ next clin­i­cal trial in which PAT-SM6 will be used in combination with Amgen’s Carfilzomib.

11/ 12 patients went on to receive addi­tional salvage ther­apy after com­plet­ing the PAT-SM6 clin­i­cal trial. Re­markably, 7/ 11 patients responded very positively with a partial response (PR) while 3 others responded with SD indicating that PAT-SM6 treat­ment may make cancer cells more sensitive to killing by other chemo­thera­peutics.

Analysis of blood samples collected during the trial con­firmed that no patient generated a sig­nif­i­cant ad­verse immune response to PAT-SM6 (immunogenicity). This is an important finding as adverse immune reac­tions to existing marketed anti­bodies is known to limit the effectiveness of these treatments.

Pharmacokinetic analysis dem­onstrated linear dose proportional in­­creases in maximum serum con­cen­tra­tion (Cmax) of PAT-SM6. Systemic exposure to the drug, dem­onstrated by area under the curve (AUCt) was in line with Cmax and showed similar linear behavior. Patients displayed apparent linear phar­ma­co­ki­netics with a rapid distribution phase followed by a slower disposition phase and a half-life of about 7 hours. The parameters of half-life, volume of distribution and clearance were consistent across the dose levels and between cycles, indicating that higher doses do not affect the general phar­ma­co­ki­netic properties of PAT-SM6.

Post treat­ment with PAT-SM6, malignant cells were isolated from the patient’s blood or bone marrow and analysed for the presence of the infused anti­body. It was shown conclusively that PAT-SM6 specifically targeted and bound to the myeloma cells. Further­more analysis of patient’s immune systems indicated that PAT-SM6 is capable of inducing an immune response by both stimulating and in­creas­ing the absolute number of CD8+, NK and regu­la­tory T-cells. These cells are specifically capable of regulating the growth and dissemination of tumours. Such changes were more significant in patients who had ex­peri­enced stable disease post treat­ment with PAT-SM6. These data may indicate specific crosstalk between PAT-SM6 and immune cells, a pre­vi­ously unreported finding that warrants further in­ves­ti­ga­tion.

Dr. Marie Roskrow, Patrys’ CEO said: “The trial results are especially exciting because they reflect single-agent activity in a dif­fi­cult-to-treat pop­u­la­tion. Due to very high rates of relapse, the combination of multiple agents is in­creas­ingly becoming a ther­apy of choice for patients with MM. Therefore, the results obtained in this trial strongly sup­port further evaluation of PAT-SM6 in combination with Carfilzomib which is the basis of our planned Amgen sponsored clin­i­cal trial.”

About Patrys Limited

Based in Melbourne, Australia, Patrys (ASX: PAB) is focused on the devel­op­ment of natural human anti­bodies as ther­a­pies for cancer and other major diseases. Patrys has a deep pipe­line of anti-cancer natural human antibodies that enable both internal devel­op­ment and partnering oppor­tu­ni­ties. More in­for­ma­tion can be found at www.patrys.com.

About PAT-SM6

PAT-SM6 is a natural human IgM anti­body which has been shown to have potent anti-cancer properties in a large number of laboratory and animal studies. More specifically, Patrys has screened PAT-SM6 against more than 200 tumours from individual patients with various cancers, and the prod­uct binds to over 90% of the tumours screened re­gard­less of cancer type or patient age, gender or disease stage. Patrys has filed patent applications to cover the PAT-SM6 anti­body molecule, disease target, and the mech­a­nism of action. Patrys’ PAT-SM6 has shown convincing evi­dence of poten­tial thera­peutic benefit in the recently com­pleted Phase I/IIa clinical trial in patients with re­lapsed and refractory multiple myeloma. PAT-SM6 has been granted orphan drug status in Europe and the USA for multiple myeloma. Patrys has also suc­cess­fully com­pleted a Phase I clin­i­cal trial to eval­u­ate PAT-SM6 as a ther­apy for mel­anoma. Patrys is now preparing for the next clin­i­cal trial (a combination study of PAT-SM6 and Carfilzomib) which is to be sponsored by Onyx Pharma­ceu­ticals, a sub­sid­i­ary of Amgen.

About GRP78

Patrys clin­i­cal can­di­date PAT-SM6 binds to a form of Glucose-regulated protein 78 (GRP78), which is ex­pressed on the surface of cancer cells but not detected on the surface of healthy cells. Once bound, the PAT-SM6/GRP78 complex is then internalised into cancer cells inducing apop­tosis and cell death. The po­ten­tial of GRP78 as a target for cancer ther­apy is sup­ported by extensive third party literature that has reported several roles played by GRP78 with respect to promoting tumour proliferation, tumour survival, metastases and resistance to a wide variety of existing anti-cancer ther­a­pies. As a result, GRP78 ex­pres­sion has been correlated with an adverse prognosis in mel­anoma, breast, lung, gastric, hepato­cellular and prostate cancer, and drug resistance in breast cancer. Given GRP78's reported roles with respect to several cancers, a molecule such as PAT-SM6 presents a promising anti-cancer treat­ment to the extent it interferes with the function of GRP78 in cancer.

Source: Patrys Limited.