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Aldatu Secures $1.5M NIH Grant to Commercialize HIV Drug-Resistance Test

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NEW YORK (GenomeWeb) – Startup Aldatu Biosciences this month received a two-year, $1.5 million grant from the National Institutes of Health to finalize development of a novel qPCR-based platform for HIV drug-resistance testing in sub-Saharan Africa.

With the support of the direct-to-Phase II Small Business Innovation Research grant, the Cambridge, Massachusetts-based company aims to develop a thermostablized version of the genotyping test, which it will initially launch in Botswana and Tanzania in partnership with research institutes and public health agencies in those nations.

Aldatu was established in 2014 to commercialize technology developed by Co-founder and CSO Iain MacLeod while he was working at the Botswana-Harvard AIDS Institute, according to Co-founder and CEO David Raiser.

In sub-Saharan Africa, clinicians primarily identify resistance to HIV drugs by treating patients with World Health Organization-recommended first-line therapy and waiting to see if they respond, he explained. However, in some cases patients don't show improvement due to their failure to take their medication properly, not drug resistance.

"This is particularly important … given that the drugs that patients are switched to are much more expensive," Raiser noted.

To address this issue, MacLeod developed a technology dubbed pan-degenerate amplification and adaption, or PANDAA, which he said overcomes the limitations of standard qPCR genotyping to enable multiplexed detection of drug resistance in about 90 minutes.

Given the variability of HIV, looking for a single nucleotide change that confers resistance using conventional probe-based qPCR will also pick up additional mismatches present in the probe-binding region, leading to false negatives, MacLeod told GenomeWeb.

Sanger sequencing, meantime, is time-consuming and lacks sensitivity, while next-generation sequencing (NGS) tends to be too complex for labs in developing nations.

"All PANDAA does is strip out all of that additional variability in the probe-binding site, but doesn't touch the resistance site of interest," MacLeod said. "PANDAA changes the probe-binding site to match the probe, and that way you get rid of … secondary polymorphisms and you can rapidly and sensitively detect resistance."

By using PANDAA, "there is value for the patients in that you're keeping [them] on drugs that are effective … [and value] for the public health system and the HIV treatment program because you are able to only switch people to more expensive drugs [when] they actually need them," Raiser added.

Aldatu has already developed a wet test based on a panel of six established drug-resistance markers, which MacLeod said are found in 99 percent of people failing first-line HIV treatment in sub-Saharan Africa. The test has been validated in individuals failing first-line regimens in Botswana and Tanzania, and been shown to work as well as MiSeq NGS.

The company also showed that the test can simultaneously detect drug resistance and quantify the total amount of virus present, Raiser said. "So it actually serves as a viral load quantification test, as well as a quantitative measure of drug-resistance variants. This is actually the first test that is able to do both of those things at the same time."

To enable the commercial roll out of the test — called PANDAA HIV6 — Aldatu is now using the NIH funding to develop a lyophilized version that is more appropriate for use in resource-limited countries.

"The primers, probes, and [other] components needed for [PANDAA HIV6] are lyophilized in the bottom of the 96-well plate," MacLeod said. With the planned kit, "the technician at the other end just has to add in the purified RNA from the sample and then run it on a qPCR machine."

Once that work is done, Aldatu aims to trial it in Botswana and Tanzania to see how it performs with end users.

Although HIV drug resistance is an issue in the US, Aldatu does not anticipate commercializing PANDAA HIV6 domestically.

"Antiretroviral drugs have been available [in the US] for longer and a broader range is available," MacLeod said. "So instead of looking for six mutations, you'd have to look at a panel of maybe 81 mutations," making an effective test far more complicated. Additionally, large laboratory service firms have already begun making significant investments in NGS technologies for drug-resistance testing.

"So there is much more of a barrier to implement PANDAA for HIV drug resistance testing in the US," he said.

Still, Aldatu expects the PANDAA technology could prove viable in the US for the detection of drug resistance to other highly pathomorphic pathogens, Raiser said. He declined to specifically name which ones the company is considering, noting that it is currently focused on PANDAA HIV6.

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