XBiotech (NASDAQ: XBIT) had a pretty good IPO, but I believe it is just a biotech bubble. The company is developing a cure-all for cancers, cachexia, vascular disease, type 2 diabetes, plaque psoriasis, and acne. Don’t expect any drug to be a cure-all.
XBiotech was founded by John Simard in 2005. Simard previously founded CTL ImmunoTherapies and AlleCure, which later merged to form MannKind (NASDAQ: MNKD). In total, XBiotech has raised $134 million since its founding.
The company believes its “True Human” mAbs have the potential to be safer and more effective than the currently marketed fully human mAbs. “True Human” means these mAbs are derived from a natural antibody identified from the blood of an individual.
MABp1 (Xilonix), XBiotech’s lead product candidate, is a anti-ILα mAb. IL1α is an inflammatory cytokine produced by leukocytes and other cells. Inflammation can indeed contribute to the development and progression of a variety of different diseases, but it doesn’t means blocking ILα can cure all these diseases. Antibodies against IL1α are expressed in about 10% of the healthy population. Schering-Plough abandoned their anti-IL1α program in 1994.
MABp1 has been administered to 170 patients in seven different clinical trials. In the 52-patient Phase I/II trial of MABp1 in metastatic cancer (18 tumour types), only one patient had a partial response. XBiotech touts that patients receiving MABp1 live longer on average than historical controls, but I think the trial was too small to support the comparison.
XBiotech has completed a Phase II trial to test MABp1 in 7 patients with type 2 diabetes. After the 60 days period of treatment, HbAlc was reduced by 0.14±0.21%. The change was not statistically significant (p=0.15). Almost all approved diabetes drugs have produced significantly higher reductions in HbA1c levels.
In the Phase II study of MABp1 in 8 patients with moderate to severe plaque psoriasis, only one patient achieved a PASI score of 75 at week 8. According to the Humira (adalimumab) label, 71% of patients achieved a PASI 75 response at week 16.
XBiotech is testing MABp1 in colorectal cancer in two Phase III trials. The European trial will enroll at least 276 patients and is expected to be completed by mid-2015. The U.S. trial was designed for 656 patients. XBiotech amended the inclusion criteria and the control arm in 2014. The enrollment has resumed with a projected completion in 2016. Prior to the protocol amendment, 40 patients had entered the study. The findings were not statistically significant due to the relatively small number of patients.
In my opinion, it is reckless to initiate such a large Phase III trial without solid proof of concept. Adam Feuerstein at TheStreet had a negative comment as well:
XBiotech’s S-1 is filled with classic biotech red flags, including lack of quality venture capital backers, D-list underwriters and dubious clinical data generated from small subsets of patients presented in ways which overestimate treatment effect.
 Front Immunol. 2015, 6, 55.
 Lancet Oncol. 2014, 15(6), 656-666.
 JAMA Dermatol. 2015, doi: 10.1001/jamadermatol.2014.5391.