SecProbe.io

CORRESP
1
filename1.htm

Response Letter

 811 Barton Springs Road

Suite 811

Austin, Texas 78704

(512) 236-9908

(512) 236-9904 (fax)

ozburn@slollp.com

August 18, 2017

 United States Securities and Exchange
Commission

 Division of Corporation Finance

 Mail Stop 4546

 100 F Street, N.E.

 Washington, D.C. 20549

Attn: Suzanne Hayes

Re:
Genprex, Inc.

Registration Statement on Form S-1

Filed July 21, 2017

File No. 333-219386

 Dear Ms. Hayes:

Enclosed on behalf of our client, Genprex, Inc. (the “Company”), is Amendment No. 1 to Registration Statement on
Form S-1 (the “Amendment”). The Amendment updates the Company’s Registration Statement on Form S-1 originally filed with the Securities and Exchange Commission (the “Commission”) on July 21,
2017 (the “Registration Statement”). The copy of the Amendment that is enclosed with the paper copy of this letter is marked to show changes from the Registration Statement.

The Registration Statement is being submitted in response to comments received from the staff of the Commission (the
“Staff”) by letter dated August 3, 2017 with respect to the Registration Statement (the “Comment Letter”) as well as to update the disclosure generally. The numbering of the paragraphs below
corresponds to the numbering in the Comment Letter, the text of which we have incorporated into this response letter for convenience. Except where otherwise indicated, page references in the text of the responses below correspond to the page numbers
of the Registration Statement.

 United States Securities and Exchange Commission

August 18, 2017

  Page
 2

 Staff Comments and Company Responses

Prospectus Summary

 Overview, page 1

1.
We note your response to comment 2, however we are unable to locate any disclosure relating to MD Anderson’s preclinical studies combining Oncoprex with MK2206. Please also revise your disclosure to state
specifically that you have not conducted any preclinical or clinical studies combining Oncoprex with pembrolizumab and atezolizumab. In addition, in your discussion in the penultimate paragraph on page 2, please clarify that your references to
clinical data refer to data from nine patients.

 Response: The Company has expanded the disclosure on page 80 of the Amendment to
include the following disclosure relating to MD Anderson’s preclinical studies combining Oncoprex with MK2206:

 “In another study, MD Anderson
researchers analyzed the effects of TUSC2 re-expression on the sensitivity of tumor cells to the AKT inhibitor MK2206 in vitro and in mice. The AKT pathway is an important intracellular, converging positive regulator of apoptosis. AKT stimulates
apoptosis and is frequently dysregulated in cancers, and this has been associated with reduced sensitivity to anti-tumor drugs. The study showed that the combination of TUSC2 transfection with MK2206 treatment suppressed tumor cell viability in
vitro and effectively inhibited xenograft tumor growth in vivo more effectively than either agent alone.”

 Response: The Company has expanded
the disclosure on pages 4 and 67 of the Amendment to include the following sentence, indicating that the Company has not conducted any preclinical or clinical studies combining Oncoprex with pembrolizumab or atezolizumab:

“We have not conducted any preclinical or clinical studies combining Oncoprex with pembrolizumab or atezolizumab.”

Response: As disclosed on pages 4 and 68 of the Amendment, the Company has enrolled a total of 28 patients in its Phase I/II clinical trial of Oncoprex
with erlotinib. Of these 28 patients, a total of 18 were enrolled in the Phase I portion of the trial, and a total of 10 were enrolled in the Phase II portion. Three of the 18 Phase I subjects were included in the Phase II portion because they had
been given the MTD in the Phase I portion of the trial and thus met the inclusion criteria for the Phase II portion. Of the 10 patients enrolled in the Phase II portion, one was not evaluated; as a result, the Company has data from nine patients in
the Phase II portion. However, data collected from the other 15 patients in the Phase I portion did show that Oncoprex can be combined with erlotinib in humans. Accordingly, the Company’s conclusion that Oncoprex can be combined with erlotinib
is based on data from a total of 24 patients, composed of 15 patients from the Phase I portion and nine patients from the Phase II portion of our Phase I/II clinical trial.

 United States Securities and Exchange Commission

August 18, 2017

  Page
 3

 Accordingly, the Company has revised the disclosure on pages 3 and 67 of the Amendment as
follows to clarify the references to clinical data:

 “Clinical data from the evaluation of 24 patients in our Phase I/II clinical trial, as well as
our preclinical data, indicate that Oncoprex can be combined with the widely used anti-cancer drug erlotinib (marketed as Tarceva® by Genentech, Inc.) in humans.”

2.
We refer to your revised disclosure in the second paragraph on page 4. Please balance your discussion regarding your observations from the Phase I trial to explain that the study was not designed to show changes in
outcomes.

 Response: The Company has revised the disclosure on pages 5, 69 and 77 of the Amendment as follows to explain that the
Phase I Monotherapy clinical trial was not designed to show changes in outcomes:

 “In 2012, MD Anderson researchers completed a Phase
I clinical trial of Oncoprex as a monotherapy. The primary objective of this Phase I trial was to assess the toxicity of Oncoprex administered intravenously and to determine the MTD and recommended Phase II dose of Oncoprex alone. Secondary
objectives were to assess the expression of TUSC2 following intravenous delivery of Oncoprex in tumor biopsies and also to assess the anti-cancer activity of Oncoprex. This trial demonstrated that Oncoprex was well tolerated and established the MTD
and the therapeutic dosage for Oncoprex at 0.06 mg/kg administered every 21 days. Although this trial was not designed to show changes in outcomes, a halt in cancer growth was observed in a number of patients, and tumor regressions occurred in
primary lung tumors and metastatic cancers in the liver, pancreas, and lymph nodes. In addition, pre- and post-treatment patient biopsies demonstrated that intravenous Oncoprex selectively and preferentially targeted patients’ cancer cells, and
suggested that clinical anti-cancer activity was mediated by TUSC2.”

 Our Pipeline, page 4

3.
We acknowledge your revised disclosure in response to comment 7. Please also remove the 3p21.3 candidate program that is shown in the preclinical phase since it does not appear that this program has advanced much
beyond the identification of certain genes that may have cancer fighting functions by researchers at MD Anderson

 Response:
Because preclinical studies of several of the 3p21.3 candidate tumor suppressor genes and their effects on lung cancer have been conducted, the Company believes that the inclusion of the 3p21.3 candidate program in the Company’s pipeline
illustration is appropriate.

 Accordingly, the Company has revised the “Our Pipeline” table on pages 6 and 70 to reduce the
length of the arrow associated with the Company’s 3p21.3 candidate program. The Company has also expanded the disclosure on pages 92 and 93 of the Amendment to include the following disclosure relating to the MD Anderson’s preclinical
studies of candidate tumor suppressor genes in the 3p21.3 chromosome sub-region:

 United States Securities and Exchange Commission

August 18, 2017

  Page
 4

 “Preclinical Studies of Additional 3p21.3 Genes with Cancer-Fighting Properties

 We have licensed rights to a group of candidate tumor suppressor genes, including 101F6, NPRL2, CACNA2D2, PL6, BLU, RASSF1, HYAL 1
and HYAL2, in addition to TUSC2 (which is also referred to as FUS1), all of which are located in a sub-region of human chromosome 3 known as 3p21.3. Using a number of techniques, MD Anderson researchers and their collaborators have identified these
genes as potentially having cancer-fighting characteristics. MD Anderson researchers have subsequently conducted a number of preclinical studies on certain of these genes, particularly 101F6 and NPRL2, as well as TUSC2, both alone and in combination
with other compounds, in order to assess their actual effects on NSCLC. Three of these preclinical studies are described below. We plan to support continuing research into the cancer-fighting properties of these and other genes in the 3p21.3
sub-region as an important part of our strategy.

 Preclinical Study Showing Expression of Several Genes in the Human Chromosome 3p21.3 Sub-region by an
Adenovirus Vector Results in Tumor Suppressor Activities in Vitro and in Vivo

 MD Anderson researchers conducted preclinical studies,
both in vitro and in vivo, of several of the licensed genes located in the 3p21.3 sub-region, in order to assess their effects on tumor cell proliferation and apoptosis in human lung cancer cells. The researchers used adenoviral vectors to introduce
individual wild-type genes into 3p-deficient tumor xenografts and tumor cell lines. This “forced expression” of the wild-type forms of TUSC2, 101F6, and NPRL2 resulted in inhibition of tumor cell growth by induction of apoptosis and/or
alteration of cell cycle pathways in vitro, compared to control. Intratumoral injection of 101F6, TUSC2 and NPRL2 with adenoviral vectors, as well as systemic administration of these genes in an experimental mouse model, suppressed the growth of
tumor xenografts (in this case, human tissue grafted onto the mouse model) and inhibited lung metastases. The results of these studies showed that the genes 101F6, NPRL2 and TUSC2 had the most significant anti-cancer effects of the tested genes and
were therefore the most promising genes for further study.

 Preclinical Study Showing that Tumor Suppressor 101F6 and Ascorbate Inhibit Non–Small
Cell Lung Cancer Growth

 One of the promising tumor suppressor gene candidates, 101F6, expresses a protein found in normal lung
bronchial epithelial cells and fibroblasts but whose function is impaired in most lung cancers. This protein is involved in the regeneration of ascorbate, a well-known antioxidant that has been tested as a supplemental therapeutic agent for human
cancer prevention and therapy. MD Anderson researchers studied the effect of 101F6 in combination with ascorbate on human lung cancer tissue, both in vitro and in vivo. In the in vitro portion of the study, 101F6 was transferred via nanoparticles
similar to our Oncoprex nanovesicles, and in combination with ascorbate, selectively targeted cancer cells and inhibited lung cancer cell growth to a greater extent than either 101F6 or ascorbate alone. In vivo, the systemic injection of 101F6
nanoparticles in mouse tail veins, together with the intra-abdominal injection of ascorbate, inhibited both tumor formation and growth in human NSCLC H322 lung cancer xenograft mouse models (P < 0.001) with greater effect than either 101F6 or
ascorbate administered alone.

 United States Securities and Exchange Commission

August 18, 2017

  Page
 5

 Preclinical Study Showing NPRL2 Sensitizes Human Non-Small Cell Lung Cancer (NSCLC) Cells to Cisplatin
Treatment by Regulating Key Components in the DNA Repair Pathway

 Another of the promising tumor suppressor gene candidates, NPRL2,
interacts with a kinase that is activated by cisplatin, an anti-cancer drug, leading to downstream activation of apoptosis in response to the presence of intracellular high-molecular weight DNA fragments, which themselves result from the breakup of
DNA molecules induced by exposure to cisplatin. Mutations in the NPRL2 gene are associated with resistance to this cisplatin-mediated apoptosis. MD Anderson researchers have conducted preclinical studies of NPRL2 with cisplatin in vitro in lung
cancer cell cultures and in vivo in an experimental mouse model of chest cavity cancer dissemination. Data from these studies suggest that the systemic introduction of the NPRL2 gene and the resulting expression of the NPRL2 protein in cancer cells
activates the DNA damage checkpoint pathway in cisplatin-resistant and NPRL2-negative cells. These studies suggest that the combination of NPRL2 and cisplatin could resensitize cisplatin nonresponders to cisplatin treatment, helping to overcome
resistance to cisplatin.”

 Business

Preclinical Studies of TUSC2 in the Immune Response to Cancer, page 80

4.
We refer to your revised disclosure regarding the figures on page 83 in response to comment 22. Please further explain the meaning of Figure A. In addition, please add back to the diagrams the labels of each of the
figures (e.g., “Figure A”).

 Response: The Company has revised the diagrams on page 91 of the Amendment to add back the
labels of each of the figures. The Company has also expanded the disclosure on pages 89 and 90 of the Amendment to include the following disclosure, in order to further explain the preclinical study and the meaning of Figure A:

“Preclinical Study Showing that TUSC2 Immunogene Therapy is Synergistic with Anti-PD1 in Lung Cancer Syngeneic Mouse Models

Based on the prolonged responses that were observed in TUSC2 clinical trials, which suggest that TUSC2 may modulate the immune response, and on
the fact that checkpoint blockade immunotherapy against PD1 and PD-L1 has yielded durable antitumor activity in a subset of NSCLC patients, MD Anderson researchers conducted a preclinical study to investigate the immune response to TUSC2 in immune
cell populations and the synergistic antitumor effect of TUCS2 in combination with anti-PD1 checkpoint blockade in syngeneic mouse NSCLC models.

Two Kras-mutant syngeneic mouse models were used to explore the effect of TUSC2+anti-PD1 (+/- anti-CTLA-4) on immune cells infiltration into
the tumor micro-environment. Activating Kras mutations are the most common driver mutations in lung adenocarcinomas. Lung cancer with mutant Kras has a poor prognosis, is often resistant to conventional therapy, and readily becomes resistant to
targeted therapies with kinase inhibitors. Studies by researchers not at MD Anderson have found that PD1 expression was highly associated with the presence of Kras mutations and that PD-L1 expression was elevated in premalignant Kras-mutant cells,
suggesting that Kras mutation may affect the function of the PD1/PD-L1 immune checkpoint pathway.

 United States Securities and Exchange Commission

August 18, 2017

  Page
 6

 The first syngeneic mouse model used a murine lung carcinoma cell line CMT/167-luc with a
Kras G12V mutation and a low level of TUSC2 expression, implanted subcutaneously in C57BL/6 mice. The second syngeneic mouse model optimized an aggressive experimental metastatic lung cancer model using 129SvE mice injected with SQ344 lung cancer
cells, which contained KrasG12D allele. The SQ344 tumor model was found to be less sensitive to anti-PD1 single agent treatment.

 The
graph below shows the protocol for and results of this preclinical study, in which anti-PD-1, TUSC2 and anti-CTLA-4 treatments were administered in the SQ344 metastatic lung tumor mouse model. Figure A shows that SQ344 tumor cells have less
expression of PD-L1 than in the CMT167 model, as determined by flow cytometry. The level of PD-L1 expression in SQ344 cells was only 4.5%, which was significantly lower than the level found in the CMT 167 mouse tumor model (23.7% vs. 4.5%, p
< 0.0001), suggesting that SQ344 would respond less strongly to an anti-PD1 agent than the CMT167 model. Figure B shows the protocol for the experiment, in which treatments were administered every three or four days in the mouse tumor cells.
Figure C shows the survival of the mice with the lung tumor cells treated with (a) no treatment, (b) a combination of anti-PD-1 and anti-CTLA-4, (c) TUSC2 alone, (d) a combination of TUSC2 and anti-PD-1, and (e) a
combination of TUSC2, anti-PD