The phase 1b WHV138 Safety Review Board (SMB) recently held their second of three period safety review meetings. The board chair, Dr. Marnie Elizaga, together with board members, Dr. Michael Keefer and Dr. Yunda Huang, as well as our study statistician Dr. Sue Li, reviewed cumulative safety data unblinded as to treatment/placebo arm and concluded that the trial can continue without any modifications based on the low-risk safety data. Overall, the trial is progressing well and already in its final stage, the 12-month post-final vaccination follow-up period. With the recent administration of the trial’s final vaccination, the third milestone for the next periodic safety review by the SMB has been met and will be conducted within the next couple of months.
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The WHV138 Trial Reaches Major Milestone: The Final Dose of the Investigational Vaccine PDPHV Has Been Administered
After about a year and half since trial initiation, the WHV138 clinical team has recently administered the trial’s final vaccination of the investigational product PDPHV, a polyvalent DNA/Protein HIV Vaccine that includes five DNA plasmids encoding for HIV Env A, B, C, AE and gag C with matched protein gp120 Env antigens. WHV138 is currently the only in-human clinical trial testing a heterologous HIV vaccine candidate that targets all four major circulating subtypes of HIV-1. The administration of the trial’s final vaccination without the occurrence of any major safety concerns thus far is therefore a promising and exiting milestone for the whole HIV vaccine research community.
The single-site, randomized, placebo-controlled phase 1b trial WHV138 started screening in June of 2021 and enrolled a total of 42 volunteers into two groups. Both groups received the DNA and the Protein products of PDPHV as a co-administration regimen in repeated doses but at slightly different vaccination schedules. While Group 1 volunteers received four doses of the DNA and the adjuvanted Protein vaccine in two different arms over the course of twelve months, Group 2 volunteers received five doses of a mix of the DNA and the Protein vaccine without an adjuvant into both arms over the course of eight months. All active volunteers will continue the trial for a 12-month safety observation period following their final vaccination.
The previously conducted phase 1a HVTN124 trial assessed the safety and immunogenicity of PDPHV using a DNA prime – Protein boost approach which has shown remarkable immune responses according to preliminary analyses that were presented at the 2022 Keystone Symposium on Next Generation HIV Vaccines and Therapies earlier last year. Exploratory immunogenicity studies of WHV138 will be conducted once the trial concludes towards the end of this year.
WHV Joins the World in Commemorating World AIDS Day 2022
United with people around the world in the fight against HIV, we at WHV reaffirm our commitment to help end the HIV pandemic with our continued efforts in developing a safe and effective HIV vaccine to significantly reduce new infections around the world. Today, the WHV team celebrates the achievements of the HIV vaccine research community in 2022 by reflecting on our accomplishments during the past 12 months:
WHV’s greatest pride this year is the progress of the phase 1b WHV138 trial, a single-site randomized controlled trial testing the safety and immunogenicity of the polyvalent DNA/Protein HIV Vaccine candidate (PDPHV) in two different treatment groups using a co-administration regimen in repeated doses. As the IND-holder of PDPHV, WHV successfully filed their first IND annual report with the FDA and passed the Safety Monitoring Board review without any safety concerns. After successfully concluding enrollment of 42 healthy volunteers in the midst of the COVID-19 pandemic, WHV138 is now approaching the finishing line in volunteer vaccinations which is followed by a 12-month safety follow-up period.
PDPHV is currently the only vaccine tested in humans with a formulation consisting of DNA-encoded gp120 antigens of four different clades (A, B, C, and AE) and matched recombinant gp120 proteins. This heterologous HIV vaccine candidate has shown promising results using a DNA prime – Protein boost regimen in the preceding phase 1a HVTN124 trial, a multi-center randomized controlled trial sponsored by the HIV Vaccine Trials Network (HVTN) and funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). Secondary analyses of HVTN124 indicate that PDPHV has the potential to elicit cross-protective, high magnitude, and large breadth immune responses. Therefore, WHV strives to quickly advance the product development program of PDPHV and has begun planning a phase 2 trial to further investigate the immunogenicity of this promising vaccine candidate. With such a low-risk safety profile and very positive preliminary immunogenicity results, PDPHV could play a major role in the worldwide HIV prevention efforts since a safe and effective preventative HIV vaccine is one of the necessary tools to control the HIV pandemic.
In addition to the clinical trial’s progress, WHV was able to help advance the HIV vaccine field by contributing to the growing body of knowledge with complex research studies resulting from WHV’s vaccine development program. With the support of renowned research partners, three different posters featuring the first- and second-generation PDPHV were presented at two major conferences this year. Two poster presentations were held at the 2022 Keystone Symposium on HIV Vaccines in March and two posters were presented at the 2022 ISV Annual Congress in September. Moreover, at the recent HVTN Full Group Meeting held in Seattle, WA in October, HVTN124 immunogenicity data were presented in a comparison analysis across multiple HVTN studies, focusing on possible correlates of protection against HIV infection. This exploratory analysis suggests that PDPHV has the strongest potential at achieving higher levels of antibody responses than any other vaccine candidate tested so far.
These preliminary data are an encouraging note that with PDPHV, the HIV vaccine field has a vaccine candidate in the pipeline with great promise to potentially be protective against HIV infection. However, additional extensive research is required to further explore these observations – a challenge that WHV and their partners are excited to dive into.
Another big milestone reached earlier this year is WHV’s move to a new research facility to accommodate their quickly progressing vaccine development program. Previously using M2D2 incubator space at the University of Massachusetts Chan Medica School (UMCMS) in Worcester, MA, where PDPHV originated from Dr. Shan Lu’s lab, WHV is now operating at a new location with much larger space and independent from UMCMS to further develop their research work.
Most recently, the WHV team was graciously welcomed into the International AIDS Society (IAS) Corporate Partnership Program as a Bronze member for the coming year. It is an honor for WHV to be working alongside world-leading HIV vaccine experts who have also joined this multi-stakeholder group that is aiming to support industry’s contribution to HIV vaccine R&D. Together, we hope to address the ongoing critical need to accelerate the development of a safe and effective HIV vaccine that can eventually be used for our ultimate goal: The prevention of new HIV infections worldwide.
WHV138 Trial Reaches New Milestone: All Group 1 Volunteers Have Received their Final Vaccination
About a year since the WHV138 trial initiation, the fourth and final vaccination was recently administered to the last volunteer of Group 1, marking a major milestone for WHV’s first phase 1b trial. Group 1 volunteers receive a co-administration of the polyvalent DNA/Protein HIV vaccine PDPHV over the course of 12 months, with the DNA and adjuvanted Protein vaccine injected intramuscularly in different arms at month 0, month 3, month 6 and month 12. This 4-dose vaccination regimen uses one dose less than the 5-dose vaccination regimen previously tested in the phase 1a trial HVTN124, in which the 5 doses were completed over the course of 8 months instead of 12. By comparing HVTN124 with WHV138, researchers are trying to assess if volunteers in WHV138 can achieve the same high level immunogenicity responses as observed in HVTN124.
Following their final vaccination, all actively enrolled volunteers are monitored for a 12-month follow-up period to ensure the safety of all study participants. The recent safety review conducted by the WHV138 Safety Monitoring Board did not identify any safety concerns.
WHV138 is a single-site randomized placebo-controlled phase 1b trial assessing the safety and immunogenicity of the second generation PDPHV, a polyvalent HIV vaccine candidate that originates from Dr. Lu’s lab at the University of Massachusetts Chan Medical School in Worcester, Massachusetts. This investigational vaccine has previously been tested under a different vaccination schedule using a DNA prime – protein boost approach in the phase 1a HVTN124 trial, which was sponsored by the HIV Vaccine Trials Network (HVTN) and funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH).
Analyses from the preceding trial HVTN124 have shown excellent safety results and very promising immunogenicity data – remarkable findings that will be published soon.
Two Posters were Presented at the 2022 ISV Annual Congress
Two organizations collaborating with WHV were given the opportunity for a poster presentation at the recent 2022 ISV Annual Congress, held in Quebec City, Canada on September 18-20 to present findings related to WHV’s product PDPHV.
One of the posters, presented by Dr. Stephen Walsh, Principal Investigator of WHV138 and a physician in the Division of Infectious Diseases at Brigham and Women’s Hospital in Boston, MA, highlights the recruitment success of WHV138. This single-site phase 1b trial has been fully enrolled with 42 volunteers after a nearly 11-month enrollment period despite the challenges imposed by the Covid19 pandemic, including the interference of Covid19 vaccination and booster needs for study volunteers who also adhere to a strict vaccination regimen of the investigational HIV vaccine product PDPHV. Electronic means of communication and data storage play a key role in the trial’s successful operations. Reaching the enrollment goal within a common recruitment time frame in the midst of the Covid19 pandemic is thanks to the use of social media platforms. By using the latest video conference tools, the team is able to hold periodic safety review meetings virtually. Moreover, regular monitoring visits are conducted through the remote review of the trial’s EDC system. These modern-day methods offer operational advantages for conducting trials in the future, even after the pandemic wanes.
The second poster showcases a study conducted at Dr. Lu’s lab at the University of Massachusetts Chan Medical School (UMMS) isolating an A32-like ADCC mediating monoclonal antibody (mAb) induced by the first generation PDPHV that was under investigation in the previous phase 1 trial DP6-001. This new mAb showed cross-clade gp120 binding and potent ADCC activities, reaching a level of magnitude like the gold standard mAb32, which was isolated from a chronically infected HIV-1 patient and serving as the ADCC benchmark in the HIV field. These findings indicate that PDPHV is capable to induce an immune response similar to that induced by HIV infection – clues that can help researchers advance towards new breakthroughs in the HIV vaccine field.
WHV’s HIV vaccine candidate PDPHV is currently the only product tested in humans that targets all four major circulating subtypes of HIV-1 responsible for the global HIV pandemic. WHV is pleased that two posters about PDPHV were presented at this year’s ISV Annual Congress.
The Phase 1b Trial WHV138 is Passing the First SMB Safety Review Meeting
The WHV138 Safety Review Board (SMB) successfully met on July 26, 2022, together with sponsor as well as protocol leadership representatives for the trial’s first periodic safety review. The board chair, Dr. Marnie Elizaga, together with board members, Dr. Michael Keefer and Dr. Yunda Huang, reviewed cumulative safety data – unblinded as to treatment arm – from trial initiation up until everyone from Group 2 received at least their first vaccination. Since there were no major safety concerns identified, the trial will continue as planned. Thanks to the highly experienced clinical team who is running WHV138 very competently, the milestone for the next periodic safety review is approaching quickly. Thus, the second of a total of three SMB meetings will likely be held in mid-September. Overall, the trial is progressing well and on track to administer the last volunteer’s final vaccination by the end of this year, with the final safety follow-up visit anticipated to be in late fall of 2023.
WHV is Proud to Join the IAS Corporate Partnership Program
At the recent AIDS2022 conference in Montreal, Canada, the International AIDS Society (IAS) formally launched the Global HIV Vaccine Enterprise Industry Partnership Group during the satellite session “Swinging into full gear: Strengthening industry engagement in HIV vaccine research and development”. This partnership – of which WHV is now a proud member – is a multi-stakeholder group aiming to support industry’s contribution to HIV vaccine R&D by addressing and minimizing barriers to engagement.
Dr. Shan Lu, the original developer of WHV’s polyvalent DNA/Protein HIV Vaccine PDPHV, attended the partnership program inaugural session at AIDS2022 on July 29th, representing WHV as an industry partner. “We cannot successfully develop an HIV vaccine unless industry and academia work closely together”, Dr. Lu’s words during the panel discussion that perfectly summarize the history behind WHV. In 2018, WHV was brought to life as a small biotech startup that licensed PDPHV from Dr. Lu’s lab at the University of Massachusetts Chan Medical School (UMMS) to advance the HIV vaccine candidate through early clinical trial testing. As part of WHV’s product development program, the new biotech company quickly became the IND holder and sponsor of the currently ongoing phase 1b WHV138 trial testing the safety and immunogenicity of PDPHV. The preceding phase 1a HVTN124 trial, which was sponsored by the HIV Vaccine Trials Network (HVTN) and funded by the National Institute of Health (NIH), successfully concluded early last year. The HVTN124 trial tested PDPHV under a different vaccine administration regimen than WHV138 and showed that PDPHV has a good safety profile with remarkable immunogenicity data. The accomplishments of WHV’s clinical partners and considering that the phase 2 grade investigational vaccine product is already manufactured and ready for subsequent clinical testing demonstrate an unprecedented success story for a small biotech company like WHV in the HIV vaccine field. “Currently, there is no other industry entity in the world like WHV whose sole dedication is to develop a safe and effective HIV vaccine”, Dr. Lu points out, highlighting the need for closer collaboration between various stakeholders focusing on vaccine discovery, development, clinical research, manufacturing, and distribution in order to efficiently move HIV vaccine candidates from the bench to the clinic and to eventually use as a much-needed tool in the fight against the global HIV pandemic.
One Third of WHV138 Group 1 Fully Vaccinated
Despite the challenges the COVID-19 pandemic poses on many clinical trials, the phase 1b WHV138 trial is making great progress. By July 9, 2022, one third of Group 1 (N=7) has completed their vaccination regimen. Thanks to the highly experienced study team at the Brigham and Women’s Hospital, the WHV138 trial continues to progress well.
After this fourth and final vaccination for Group 1, which is 12 months post the first vaccination, the study participants will be followed for a 12-month safety observation period before they have officially completed the study. The remaining two thirds of volunteers in Group 1 are expected to complete their full course of vaccination by the end of August.
Group 2 is also making good progress. Participants in this group receive five vaccinations over the course of 8 months, also followed by the 12-month safety observation period. In this group, all volunteers have already received their first and second vaccination. The very final vaccination is anticipated to be administered in December 2022.
WHV is proud to be partnering with such an experienced clinical team and would like to acknowledge the remarkable contribution of volunteers in the middle of new COVID-19 waves in the country.
The Phase 1b Trial WHV138 is Fully Enrolled
Thanks to our highly experienced clinical team, the enrollment objective of a total of 42 study participants has been completed. With the recent enrollment of the 21st healthy volunteer into Group 2, the single-site WHV138 trial is now fully enrolled after 10 months of assiduous recruitment efforts. This marks a major milestone for the young biotech company WHV, who is a first-time IND holder and the sponsor of this phase 1b randomized, placebo-controlled trial.
As the vaccination regimen for Group 2 includes five vaccinations over the course of 8 months, the trial’s very last vaccination will be administered by late-December of this year, followed by a 12-month safety observation period. Thus, we can anticipate the entire trial to be completed before the end of 2023. So far, there have been no major safety concerns identified. Data analyses regarding the immunogenicity of the vaccine candidate PDPHV as used in WHV138 will follow and are expected to give additional insights into the very promising immunogenicity profile generated by the HVTN124 study – a previously conducted phase 1a trial testing PDPHV under a slightly different vaccination regimen.
PDPHV is currently the only vaccine formulation tested in humans that includes viral ENV antigens from all four major circulating HIV clades with the potential to elicit very promising immune responses without any major safety concerns. WHV is therefore eager to move their HIV vaccine candidate further through the next testing stages to explore vaccine efficacy. The team has already started to prepare for a larger scale study and is hoping to officially announce trial partners in the near future.
HIV Vaccine Awareness Day 2022 – A Day to Recognize the Many Stakeholders Working to Find a Vaccine to End the HIV Pandemic
Today, on HIV Vaccine Awareness Day 2022, WHV would like to thank their partners for their crucial role in the vaccine development program of WHV’s second generation HIV vaccine candidate PDPHV. A team comprised of renowned HIV vaccine research groups, competent CROs, and talented individual specialists has been providing WHV with high quality products and expertise, assuring a smooth operation for the new biotech company over the past four years. WHV is grateful for their continued partnership and support, which has been essential in successfully moving PDPHV through the subsequent clinical testing phases.
More importantly, WHV wants to extent their gratitude towards the many volunteers who participated and continue to participate in the HIV vaccine trials, including HVTN124 and WHV138. Without all of the healthy individuals who volunteer as a research subject, the search for a safe and effective preventative HIV vaccine would not be possible. As the phase 1b WHV138 trial is almost fully enrolled, the investigation of the safety and immunogenicity of this polyvalent DNA/Protein HIV vaccine candidate is progressing well. Once the trial is completed and data can be analyzed, newly acquired knowledge from this study will help the entire HIV vaccine field advance towards finding a safe and effective HIV vaccine.